THE  NEWER  PHYSIOLOGY 

IN    SURGICAL  AND 


,::>  k '  r 


THE    NEWER    PHYSIOLOGY 

IN     SURGICAL    AND     GENERAL 

PRACTICE 


First  Edition,  September,  ign. 

Second  Edition,    Revised,    A  fay,    iqis. 

Reprinted,  December,  IQI2. 

Third  Edition,    June,    IQI4. 


THE    NEWER   PHYSIOLOGY 

IN   SURGICAL 
AND  GENERAL  PRACTICE 


By   A.  RENDLE  SHORT, 

M.D.,  B.S.,  B.Sc.  (Lond.).  F.R.C.S.  (Eng.), 

Hunterian  Professor \  Royal  College  of  Surgeons ;  Examiner  in  Physiology  for 

the  F.R.C.S.;  Hon.  Assistant  Surgeon,  Bristol  Royal  Infirmary; 

Senior  Demonstrator  of  Physiology,  University  of  Bristol. 


Third  Edition 
Revised  and  Enlarged 


NEW   YORK 
WILLIAM  WOOD  AND   COMPANY 


MDCCCCXV 


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U     3 

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•***»# 

PREFACE    TO    THIRD    EDITION 

Readers  of  the  first  edition  of  this  book  will  find 
that  approximately  half  of  the  present  volume  is 
new,  hence  the  change  in  title.  Large  sections  have 
been  omitted  to  make  room  for  these  additions 
without  greatly  increasing  the  size  of  the  book. 

In  the  third  edition,  new  chapters  are  introduced 
on  vitamines  and  the  genital  glands  ;  the  articles 
on  surgical  shock,  the  digestive  apparatus,  the 
pituitary  and  pineal  glands,  and  on  chloroform 
poisoning  are  largely  rewritten.  There  are  also 
important  additions  to  the  chapters  on  the  thyroid 
gland  and  the  physiology  of  the  spinal  cord,  besides 
minor  changes  elsewhere. 

A.  R.  S. 

June,  1914. 


PREFACE    TO    FIRST    EDITION 

These  chapters  are  intended  for  the  general  practi- 
tioner, the  consulting  surgeon,  and  candidates  for 
the  higher  examinations  in  physiology. 

There  was  a  time  when  one  man  could  be  physio- 
logist and  surgeon  too,  but  the  rapid  march  of 
progress  in  each  field  has  left  a  great  gap  between 
the  sciences  which  is  continually  widening.  The 
triumphs  of  the  surgeon  are  unknown  to  the  physio- 
logist, and  the  converse  is  equally  true.  Yet  many 
of  the  discoveries  of  the  past  ten  years  which  have  so 
changed  the  face  of  physiology  are  fraught  with  vast 
possibilities  for  the  clinician.  This  book  is  an  attempt 
to  sift  out  from  the  New  Physiology  that  which  is 
likely  to  be  of  value  in  the  actual  diagnosis  and 
treatment  of  patients. 

It  would  be  a  small  service  to  lay  before  the 
practical  reader  mere  theories  or  guess-work.  With 
but  few  exceptions,  only  the  established  and  settled 
conclusions  arrived  at  by  many  competent  and 
independent  workers  have  been  introduced.  Part 
of  the  chapter  on  cutaneous  anaesthetics  and  a  few 
other  researches  and  passing  suggestions  for  which 
the  author  is  personally  responsible  must  stand  in 
a  different  category. 


viii  PREFACE 

An  effort  has  been  made  to  explain  matters  so 
simply  that  they  may  be  intelligible  to  those  having 
the  most  elementary  knowledge  of  physiology,  and 
all  technical  terms  have  been  avoided  or  defined. 

There  are  excellent  manuals  now  published 
treating  of  the  application  of  physiology  to  diseases 
which  principally  concern  the  consulting  physician. 
This  little  book  limits  itself  to  surgical  problems,  and 
to  the  common  every-day  aspects  of  disease  that 
confront  us  all,  physicians,  surgeons,  and  general 
practitioners  alike. 

I  owe  a  debt  of  thanks  to  my  chief,  Professor 
A.  F.  Stanley  Kent,  for  some  valuable  suggestions 
and  criticisms. 

A.  R.  S. 

Bristol, 

September,  191 1. 


CONTENTS 

:hapter  page 

I. — VlTAMINES  .....  i 

Beri-beri. — Growth. — Scurvy. — Rickets. 

II. — The  Genital  Glands  7 

Functions  of  the  ovary. — Functions  of  the 
testis. — Control  of  the  genital  glands  by  internal 
secretions. — The  secretion  of  milk. — The  ovum. 
Chemical  diagnosis  of  pregnancy. 

III. — Surgical  Shock  -  -  -  -         21 

The  exhausted  vasomotor  centre  theory  of 
Crile  and  Mummery. — The  acapnia  theory  of 
Yandell  Henderson. — The  oligsemia  theory  of 
Cobbett  and  Vale. — The  adrenalin  exhaustion 
theory. — The  nature  of  surgical  shock  ;  its 
diagnosis,  treatment,  and  prevention. — Intra- 
venous saline  transfusion. 

IV. — The  Growth  of  Bone  -  -  56 

Recent  change  in  our  conception  of  the  growth 
of  bone. — Osteoblasts. — Increase  in  the  length 
of  bone. — Increase  in  the  girth  of  bone. — Func- 
tion of  the  periosteum. — The  regenerative 
powers  of  bone. — Transplantation  of  bone. — 
Application  of  modern  researches  to  surgical 
practice. — Relation  of  the  ductless  glands  to  the 
growth  of  bone. 

V. — The  Thyroid  and  Parathyroid  Glands      -         69 

History. — Removal  of  the  thyroid  and  para- 
thyroids.— Removal  of  the  parathyroids  alone. 
— Removal  of  the  thyroid  alone. — Thyroid 
feeding. — Chemistry  of  thyroid  colloid. — 
Parenchymatous  goitre. — Iodoform  and  thy- 
roidism. — Action  of  iodides  on  gummata  and 
atheroma.  —  Exophthalmic  goitre.  —  Practical 
deductions. 


x  CONTENTS 

CHAPTER  PAGE 

VI. — The  Pituitary  and  Pineal  Glands  -  -        88 

The  effects  of  removal  in  animals. — Injection 
of  extracts  ;  pituitary  feeding. — Acromegaly 
and  gigantism. — Frohlich's  type. — Functions 
of  the  pituitary  gland. — Therapeutic  value  of 
pituitary  extract. — The  pineal  gland. 

VII. — Studies  in  Digestion  and  Absorption         -        98 

Movements  of  digestion. — Sensation  in  the 
alimentary  canal. — Causes  of  variation  in  the 
hydrochloric  acid  of  gastric  juice. — The  physio- 
logical effects  of  gastrojejunostomy. — Feeding 
after  gastrostomy. — The  process  of  secretion  of 
pancreatic  juice. — The  bile. — The  absorption  of 
proteins. — Absorption  in  the  large  intestine. — 
The  value  of  nutrient  enemata. 

VIII. — The  Hemorrhagic  Diathesis  -  -       131 

The  physiology  of  the  coagulation  of  the 
blood. — Fibrinolysis.— ^Haemophilia. — Pathology 
of  haemophilia. — Treatment  of  haemophilia. — 
The  therapeutics  of  calcium  salts. 

IX. — The  Physiology  of  Uric  Acid  and  other 

Urinary  Deposits  -  -  -       145 

Uric  acid. — Derivation  from  food-stuffs. — 
Derivation  from  the  tissues. — The  purin  bodies. 
— Calcium  oxalate. — Cystin. 

X. — Acidosis,  Acetonemia,  and  Diabetes  -       157 

Conditions  of  occurrence  of  acetone,  diacetic 
acid,  and  /3-oxybutyric  acid. — Origin  from  fats. 
— Sugar  starvation  the  cause  of  acidosis. — Acid 
poisoning. — The  diagnosis  of  starvation. — The 
essential'  nature  of  diabetes.— The  treatment  of 
non-diabetic  acidosis. — The  prevention  of  post- 
operative coma  in  diabetics. 

XI. — Immediate     and     Remote     Poisoning     by 

Chloroform  .-.-■-       177 

Sudden  death  under  chloroform. — The  fatal 
adrenalin-chloroform    combination. 


CONTENTS 


XI 


CHAPTER  PAGE 

XII. — Nerve  Injuries  ....       184 

The  effects  of  nerve  section. — Epicritic, 
protopathic,  and  deep  sensibility. — Causation 
of  trophic  lesions. — Diagnosis  of  partial  nerve 
section. — How  degenerated  nerve  is  regenerated. 
— The  results  of  primary  and  secondary  nerve- 
suture. — Methods  of  dealing  with  wide  gaps. 

XIII. — The  Surgical  Physiology  of  the  Spinal 

Cord  -----       199 

The  effects  of  division  of  the  posterior  nerve 
roots. — The  diagnosis  and  localization  of 
tumours  of  the  spinal  cord. — The  exact  dia- 
gnosis of  injuries  of  the  spinal  cord. 

XIV. — Cerebral  Localization  -  -  -       213 

The  causation  and  significance  of  optic 
neuritis. — Localization  in  the  cerebellum. — 
Tumours  in  the  cerebello-pontine  angle. — 
Localization  of  sensation  in  the  cerebral  cortex. 
— Functions  of  the  frontal  cortex  ;  spasticity. 
— Apraxia.  —  Aphasia. — Misleading  localizing 
signs  of  cerebral  tumour. — The  cerebrospinal 
fluid. 

XV. — The  Action  of  Cutaneous  Anaesthetics     •       239 
Drugs  applied  to  the  unbroken  skin. 

APPENDIX. — Absorption   of  Nitrogen  from 

Amino-acids  -  245 


The  Newer  Physiology  in 
Surgical  and  General  Practice 


CHAPTER   I. 

VITAMINES. 

Beri-beri — Growth — Scurvy — Rickets. 

FOR  generations  it  has  been  a  fundamental 
axiom  of  dietetics  that  a  proper  food  allow- 
ance should  contain  proteins,  carbohydrates,  fats, 
salts,  and  water.  Tables,  such  as  Ranke's,  have 
been  drawn  up  and  copied  from  book  to  book, 
setting  forth  the  proper  proportions  of  each  to 
maintain  health.  During  the  past  year  or  two, 
however,  important  evidence  has  been  adduced  to 
show  that  these  five  proximate  principles  by  them- 
selves are  inadequate,  and  that  a  mysterious  some- 
thing more  is  necessary. 

One  of  the  first  reforms  leading  up  to  the  marvellous 
emancipation  of  modern  Japan  from  her  mediaevalism 
of  half  a  century  ago  was  concerned  with  a  problem 
of  this  sort.  The  Japanese  navy  was  reduced  to 
complete  ineptitude  by  the  prevalence  of  beri-beri — 
a  form  of  peripheral  neuritis — amongst  the  crews,  as 

I 


2  VITAMINES 

many  as  a  quarter  of  the  men  being  afflicted.  Baron 
Takaki,  lately  returned  to  his  own  country  after  a 
study  of  modern  medicine,  found  that  the  dietary 
was  very  imperfect,  and  instituted  an  improved 
ration  with  complete  success.  Beri-beri  is  still  a 
terrible  scourge  amongst  the  inhabitants  of  the 
Malay  States ;  is  often  seen  in  coolies  at  English 
seaports ;  and  has  broken  out  in  an  asylum  in 
Dublin.  Improving  the  allowance  of  food  in  the 
prisons  of  the  Straits  Settlements  has  failed  to  limit 
the  disease. 

The  outstanding  feature  of  the  incidence  of  beri- 
beri in  the  Straits  is,  that  while  the  Tamils  are  exempt, 
the  Chinese  suffer  severely.  Rice  is  the  main  article 
of  diet  with  both  races,  but  with  this  difference, 
that  whereas  the  Tamils  store  their  rice  and  boil  it  in 
husk,  the  Chinese  use  husked  rice  such  as  we  are 
accustomed  to  in  this  country,  though,  of  course, 
with  us  rice  is  a  very  much  less  important  item  in  the 
daily  dietary.  The  Chinese  are  extremely  prone  to 
beri-beri ;  the  Tamils  very  seldom  suffer.  This 
cannot  be  due  to  any  racial  peculiarity,  because 
Tamils  in  prison  and  fed  on  husked  rice  are  just  as 
liable  as  the  Chinese. 

The  explanation  usually  given  has  been  that  the 
bare  rice  grain  becomes  contaminated  in  some  way  ; 
but  recent  experiments  by  Casimir  Funk  and  others 
bring  out  another  aspect  of  the  case.  It  is  possible 
in  pigeons  to  produce  a  peripheral  neuritis  closely 
resembling  beri-beri  by  feeding  exclusively  on 
polished  rice,  and  when  small  quantities  of  husk  are 
added    the    birds    rapidly    recover.     The    essential 


VITAMIN  ES  3 

constituent  of  the  husk  which  has  this  effect  is  only 
present  in  small  quantity,  but  it  can  be  isolated  in 
crystalline  form,  and  on  analysis  appears  to  belong 
to  the  pyrimidine  group.  Milk,  yeast,  and  ox-brain 
all  contain  this  mysterious  substance,  as  well  as  rice- 
husk,  and  will  cure  the  neuritis.  From  ioo  kilos  of 
yeast  2-5  grams  of  the  crystals  were  obtained. 

There  is  clinical  evidence  in  support  of  this  experi- 
mental work.  Research  in  the  Philippines  has  shown 
that  the  infant  of  a  mother  fed  on  polished  rice  is 
likely  to  develop  beri-beri,  but  that  it  is  rapidly  cured 
either  by  fresh  cow's  milk  or  by  an  extract  of  rice- 
husk.  The  substitution  of  parboiled  for  polished 
rice  in  a  Siam  prison  has  brought  down  the  death- 
rate  from  113  to  nil. 

The  principle  having  been  once  established  that  a 
dietary  to  maintain  health  must  contain,  in  addition 
to  the  five  well-known  elements,  proteins,  carbo- 
hydrates, fats,  salts,  and  water,  traces  of  other  so-far 
unrecognized  chemicals,  a  new  field  is  opened  for 
exploration,  and  several  diseases  come  up  for  a 
similar  explanation.  The  new  chemical  bodies  which 
appear  to  be  thus  needful  are  called  "  vit amines." 

Hopkins  has  lately  shown  that  something  of  the 
sort  is  necessary  for  ordinary  growth.  Young  rats 
fed  on  purified  protein,  carbohydrate,  fat,  salts,  and 
water,  absolutely  cease  to  grow,  even  if  the  quantity 
supplied  is  correct.  If  only  a  teaspoonful  of  milk  is 
supplied  daily,  growth  becomes  normal.  Even 
sarcoma-cells  require  vitamines,  and  if  they  are  with- 
held, Jensen's  rat  sarcoma  only  develops  at  a  quarter 
its  usual  rate.     At  Romney  there   are  two   fields, 


4  VITAMINES 

apparently  identical,  but  the  animals  pasturing  in 
the  one  put  on  flesh,  and  in  the  other  they  become 
thin. 

It  has  been  known  for  centuries  that  scurvy  is  a 
deficiency  disease  ;  but  exactly  where  the  deficiency 
lies  has  always  been  uncertain.  In  days  gone  by, 
sailing  ships  on  long  voyages  were  full  of  scurvy,  the 
crews  being  thoroughly  incapacitated  by  it,  and 
many  expeditions  failing  in  consequence.  When  it 
became  compulsory  by  law  to  carry  fresh  vegetables 
and  lime  or  lemon  juice,  the  disease  became  a  thing 
of  the  past.  It  broke  out  during  the  siege  of  Paris. 
Nowadays  it  is  very  rare  in  adults  in  this  country, 
though  the  writer  has  seen  one  case  affecting  a  lonely 
man  who  was  trying  to  live  on  his  old  age  pension. 
Arctic  and  Antarctic  explorers  still  suffer,  and  both 
Captain  Scott's  expeditions  have  given  rise  to  cases  ; 
but  Nansen  found  that  fresh  meat,  even  without 
vegetables,  is  sufficient  to  prevent  it ;  and  members 
of  Scott's  and  Shackleton's  parties  proved  the 
truth  of  this.  Monkeys  can  be  given  scurvy  by 
feeding  on  stale  meat. 

Much  more  commonly  the  disease  is  seen  in  young 
infants  fed  upon  boiled,  stale,  or  artificially-prepared 
milk.  It  is  said  that  if  the  milk  is  bottled  first  and 
only  just  raised  to  boiling  point,  so  that  no  precipitate 
is  lost,  scurvy  does  not  occur.  It  is  quite  easy  to 
prevent  or  cure  it  by  giving  grape  or  orange  juice 
frequently. 

Many  suggestions  have  been  made  as  to  the  exact 
nature  of  the  deficiency  in  scurvy,  the  citrates,  mal- 
ates,  and  other  alkaline  salts  being  specially  blamed  ; 


VITAMINES  5 

but  these  will  not  cure  or  prevent  the  disease.  It  was 
said  that  calcium  citrate  was  precipitated  from  milk 
by  boiling,  but  evidently  this  cannot  be  the  explana- 
tion when  citrates  fail  to  control  scurvy.  Hoist  and 
Frohlich  have  imitated  the  symptoms  in  guinea-pigs 
by  confining  them  to  a  grain  diet ;  they  are  rapidly 
cured  by  fresh  vegetables  or  fresh  milk.  Milk  heated 
to  700  is  still  efficient ;  if  kept  at  980  for  ten  minutes 
the  antiscorbutic  power  is  lost.  No  doubt  a  vitamine 
is  destroyed.  Probably  this  vitamine  may  fail  at 
the  end  of  a  long  lactation,  even  in  fresh  human  milk, 
thus  accounting  for  a  few  authentic  cases  of  scurvy 
in  breast-fed  babies. 

The  bodies  in  milk  which  protect  against  scurvy 
and  against  beri-beri  are  not  identical.  They  differ 
in  their  reaction  to  heat.  All  vit amines  appear  to  be 
delicate  substances  which  are  lost  in  the  process  of 
keeping. 

Rickets  is,  no  doubt,  another  deficiency  disease. 
The  infants  have  usually  been  fed  upon  a  diet  con- 
taining too  much  starch  and  sugar,  and  too  little  fat 
and  protein.  The  observations  of  Bland-Sutton  at 
the  London  Zoo  rather  point  to  the  deficiency  of  fat 
as  being  the  more  important.  A  lioness  there  was 
unable  to  suckle  for  long,  and  litter  after  litter  of  cubs 
had  died  of  rickets.  Investigation  of  the  diet  showed 
that  they  were  fed  upon  London  cab-horse,  which 
naturally  did  not  supply  any  fat,  and  their  little 
teeth  were  not  able  to  crush  the  bones  and  obtain  the 
marrow.  When  they  were  given  milk,  cod-liver  oil, 
and  pounded  bones  they  did  excellently.  It  is  well 
known,  of  course,  that  cod-liver  oil,  cream,  and  fresh 


6  VITAMINES 

milk  are  the  best  treatment  for  rickets.  We  must 
wait  for  further  observations  before  deciding  whether 
the  pathology  of  the  disease  is  simply  fat  starvation, 
or  whether  the  patients  have  been  deprived  of  a 
necessary  vitamine. 

REFERENCES.* 

Funk. — Brit.  Med.  Jour.,  1913,  i,  p.  814  ;    and  articles  in 

Journal  of  Physiology,  1911-1913. 
Hopkins. — Proc.   Royal  Soc.   Med.,    vol.   vii,    Nov.,    1913  ; 

Therapeutical  Section,  p.  1. 


*  References  at  the  end  of  chapters  are  not  meant  to  be  exhaus- 
tive. Only  a  few  accessible  authorities  are  quoted,  in  some  of 
which  a  fuller  bibliography  will  be  found. 


CHAPTER    II. 
THE     GENITAL     GLANDS. 

Functions  of  the  ovary — Functions  of  the  testis — Control  of  the 
genital  glands  by  internal  secretions — The  secretion  of  milk — 
The  ovum — Chemical  diagnosis  of  pregnancy. 

STUDENTS  of  physiology  do  not  usually  devote 
as  much  attention  to  the  functions  of  the 
reproductive  apparatus  as  the  clinical  importance  of 
the  subject  demands,  and  writers  of  text-books  have 
been  in  the  habit  of  relegating  it  to  a  very  brief 
chapter  at  the  end  of  the  book. 

FUNCTIONS     OF     THE     OVARY. 

The  functions  of  the  ovary  may  be  classed  under 
three  headings  :  the  production  of  ova,  the  control 
of  menstruation,  and  the  internal  secretion.  The 
corpus  luteum  has  other  functions,  to  be  considered 
separately. 

The  ovary  shows  on  microscopical  examination 
ripe  and  unripe  ova,  the  former  enclosed  in  the 
Graafian  follicles,  corpora  lutea  of  varying  age,  and 
certain  glandular  interstitial  cells  which  probably 
furnish  the  internal  secretions,  and  are  supposed  to 
be  the  starting  point  of  multilocular  cystic  disease  of 
the  ovary.     We  shall  consider  menstruation  first. 

Menstruation. — We  shall  not  discuss  the  histology 
of  this  process,  except  to  say  that  the  mucous  mem- 


8  THE    GENITAL    GLANDS 

brane  of  the  uterus  becomes  greatly  thickened  and 
engorged  every  month,  and  haemorrhages  take  place 
into  it  which  carry  away  parts  of  the  superficial 
layers.  We  are  as  far  as  ever  from  understanding 
the  real  value  of  its  occurrence.  According  to  Blair 
Bell,  a  large  quantity  of  calcium  salts  accumulate 
in  the  blood,  which  menstruation  removes,  menstrual 
blood  being  very  rich  in  calcium. 

There  is  no  doubt  that  menstruation  is  determined 
by  an  internal  secretion  from  the  ovaries,  and  when 
these  are  both  removed  it  almost  invariably  ceases. 

Marshall  and  Heape  have  shown  that  the  process 
is  by  no  means  peculiar  to  the  human  subject.  In 
a  great  variety  of  animals,  such  as  deer,  dogs,  sheep, 
and  monkeys  there  is  a  regular  cycle  of  changes 
leading  up  to  the  oestrum  or  rut,  and  after  great 
overgrowth  of  the  mucous  membrane  of  the  uterus 
there  is  a  mucous  and  often  bloodstained  discharge 
followed  by  a  brief  period  of  fertility. 

Ovulation. — The  rupture  of  the  Graafian  follicle 
and  shedding  out  of  the  ovum  is  called  ovulation. 
It  has  been  much  debated  whether  the  time  of 
ovulation  coincides  with  that  of  menstruation  in  the 
human  subject.  In  the  animals  above  described  no 
doubt  this  is  true,  and  the  age-limits  of  fertility  and 
of  menstruation  are  approximately  the  same.  Never- 
theless the  relationship  cannot  be  exact,  because 
pregnancy  has  occurred  before  the  first  menstruation, 
and  observations  on  the  ovaries  during  abdominal 
operations  at  various  times  in  the  menstrual  cycle 
show  that  although  ovulation  commonly  takes  place 
at  about  the  same  time  as  menstruation,  this  is  by 


THE    GENITAL    GLANDS  9 

no  means  invariable.  If  it  were  so,  the  Jewish  race 
would  probably  have  become  extinct,  because,  iu 
obedience  to  the  Levitical  law,  amongst  strict  Jews 
husband  and  wife  live  apart  during  and  for  some 
days  after  menstruation. 

There  is  some  evidence  that  in  primitive  man 
there  was  only  one  annual  period  of  special  fertility. 
There  is  a  Javan  tribe  amongst  which  all  the  births 
are  said  to  take  place  in  February.  Many  animals 
that  in  the  wild  state  only  go  into  oestrum  once  or 
twice  a  year  become  fertile  all  the  time  in  captivity. 

After  bilateral  removal  of  the  ovaries  the  patient 
is  of  course  sterile  and  menstruation  ceases,  but  in 
a  few  rare  cases,  apparently  owing  to  abnormal 
outlying  fragments  of  ovary  remaining  behind, 
pregnancy  has  occurred  and  menstruation  continued. 

By  some  mysterious  chemical  attraction,  the  shed 
ovum  finds  its  way  into  the  Fallopian  tube.  If  one 
tube  is  blocked,  the  other  may  receive  the  ovum, 
because  cases  are  not  very  infrequent  of  a  tubal 
pregnancy  on  one  side  with  the  corpus  luteum  in  the 
opposite  ovary. 

There  appears  to  be  in  some  families  a  hereditary 
tendency  at  each  ovulation  to  rupture  several 
Graafian  follicles  and  shed  out  more  than  one  ovum 
at  a  time.  A  case  was  recently  reported  of  a  woman, 
aged  35,  who  had  two  sets  of  quadruplets,  three  sets 
of  triplets,  and  five  sets  of  twins.  Her  mother  had 
twenty-eight  children,  and  her  grandmother  twenty- 
nine,  including  quadruplets  and  triplets.  In  another 
case  a  woman  had  four  twin  pregnancies,  her  mother 
and  aunt  one  each,  and  her  grandmother  two. 


10  THE    GENITAL    GLANDS] 

Internal  Secretions  of  the  Ovary. — One  internal 
secretion  controls  menstruation.  Another,  or  the 
same,  appears  to  act  upon  the  vasomotor  system ; 
when  it  is  withdrawn  by  artificial  removal  of  the 
ovaries  or  by  the  cessation  of  their  function  at  the 
menopause,  the  patient  often  suffers  from  flushings, 
headaches,  and  other  neuroses. 

Under  these  same  circumstances  the  breasts, 
uterus,  and  vagina  atrophy,  and  obesity  may  develop. 
The  influence  over  breast  tissue  extends  even  to 
cancerous  tumours  growing  in  it ;  double  oophor- 
ectomy in  a  considerable  number  of  cases  of  inoperable 
cancer  has  caused  retrogression  of  the  growth,  and 
once  or  twice,  apparently,  a  cure  has  resulted.  On 
the  other  hand,  pregnancy  shortly  after  removal  of 
cancerous  breast  usually  leads  to  recurrence,  and 
during  pregnancy  a  cancer  of  the  breast  grows  with 
frightful  rapidity. 

We  do  not  possess  much  information  as  to  the 
consequences  of  removal  of  both  ovaries  in  little 
girls.  A  statement  appears  in  some  books  that  the 
operation  is  performed  in  Persia,  and  that  women  of 
a  masculine  type  result,  but  this  is  a  traveller's  tale. 

The  symptoms  of  the  artificial  menopause  following 
double  oophorectomy  may  be  much  relieved  by 
grafting  a  piece  of  the  patient's  ovary,  or  less  satis- 
factorily, that  from  another  person,  into  the 
abdominal  wall.  In  some  cases  menstruation  has 
remained  unaffected,  and  when  the  graft  has  been 
into  the  peritoneum,  it  is  said  that  pregnancy  has 
occurred.* 

♦See  Archiv.  gen.  chirurg.,  1911,  p.  550. 


THE    GENITAL    GLANDS  11 

The  Corpus  Luteum.  —  After  ovulation  has 
occurred,  the  Graafian  follicle  becomes  converted 
into  a  gland  containing  a  yellow  fatty  pigment,  the 
corpus  luteum.  Ordinarily  this  is  quite  small ;  if 
pregnancy  follows  it  may  reach  a  diameter  of  half  to 
three-quarters  of  an  inch.  Apparently  the  internal 
secretion  of  this  body  determines  the  fixation  of  the 
ovum  in  the  uterus,  and  perhaps  also  the  subsequent 
overgrowth  of  that  organ.  If  both  ovaries  are 
removed  early  in  pregnancy,  abortion  always  follows. 
In  extra-uterine  pregnancy  the  uterus  enlarges 
although  the  foetus  is  not  inside  it.  Removal  of  both 
ovaries  in  animals  or  in  the  human  subject  in  the 
later  months  of  pregnancy  does  not  usually  lead  to 
abortion  ;  one  patient  went  on  to  full  term  in  spite 
of  double  oophorectomy  as  early  as  the  sixth  week. 

Whether  the  internal  secretions  of  the  ovary  are 
due  to  the  corpus  luteum  or  to  the  interstitial 
glandular  cells  is  quite  uncertain.  There  is  some 
evidence  of  other  obscure  internal  secretory  functions 
besides  those  mentioned.  A  rare  disease  called 
osteomalacia,  characterized  by  softening  and  bend- 
ing due  to  decalcification  of  the  bones,  makes  great 
progress  during  pregnancy,  and  in  some  cases  at 
least  is  cured  by  a  double  oophorectomy. 

Ovarian  feeding  has  been  tried  to  relieve  the 
symptoms  of  the  natural  or  artificial  menopause,  but 
the  results  are  dubious.  It  is  always  difficult  to 
foretell  when  an  internal  secretion  will  be  capable  of 
absorption  through  the  intestinal  wall  unchanged. 
Calcium  salts  have  been  used  for  the  same  troubles, 
and  in  some  cases,  at  least,  work  remarkably  well. 


12  THE    GENITAL    GLANDS 

FUNCTIONS     OF     THE     TESTIS. 

The  most  obvious  function  of  the  testis,  of  course, 
is  to  produce  spermatozoa,  which  it  continues  to  do 
well  on  into  old  age. 

The  testis,  however,  contains  other  secretory  cells 
between  the  tubules,  sometimes  called  the  cells  of 
Leydig,  and  to  these  is  attributed  the  production  of 
an  internal  secretion.  It  is  not  uncommon  for  one 
or  both  testes  to  fail  to  descend  (cryptorchism),  and 
in  bilateral  cases  the  individual  is  nearly  always 
sterile,  but  the  secondary  sexual  characters  are 
usually  preserved.  On  microscopical  examination 
the  tubules  are  little  developed,  but  the  interstitial 
cells  of  Leydig  appear  to  be  normal. 

It  has  been  much  debated  whether  the  failure  to 
descend  is  the  cause  or  the  consequence  of  the  failure 
to  develop,  and  on  the  answer  to  this  question 
depends  the  surgical  treatment ;  if  the  first  is  true, 
it  is  highly  desirable  to  find  some  operative  procedure 
which  will  ensure  the  testis  a  permanent  resting- 
place  in  the  scrotum,  but  the  evidence  goes  to  show 
that  this  does  not  lead  to  proper  growth  of  the  gland, 
so  we  must  conclude  that  descent  fails  because  it  is 
not  worth  while  for  the  gubernaculum  to  bring 
down  a  defective  organ. 

When  the  testes  on  both  sides  are  removed  after 
puberty,  the  consequences  are  sterility,  atrophy  of 
the  prostate  gland,  and  in  a  few  cases  in  old  men 
mental  impairment.  The  secondary  sexual  characters 
are  not  lost,  and  it  is  very  doubtful  if  the  dotage 
which  has  sometimes  followed  is  really  due  to  loss  of 
any  internal  secretion  or  nervous  influence  ;    most 


THE    GENITAL    GLANDS  13 

probably  it  is  merely  the  consequence  of  a  mutilating 
operation  preying  on  the  mind  of  a  broken-down 
individual.  In  younger  and  healthier  adults  there 
is  no  mental  change  or  loss  of  capacity. 

The  atrophy  of  the  prostate  is  not  constant,  but 
the  effects  of  castration  have  been  taken  advantage 
of  to  reduce  the  size  of  a  prostatic  enlargement 
causing  obstruction.  Ligature  or  excision  of  the  vas 
deferens  blocks  the  way  for  the  external  secretion 
of  the  testis,  and  leads  to  atrophy  of  the  tubules 
and  consequent  sterility,  but  the  internal  secretion 
of  the  interstitial  cells  is  not  affected  unless  the 
main  vessels  of  the  cord  are  tied. 

In  boys,  the  results  of  castration  are  more  far- 
reaching,  causing  not  only  sterility  but  also  failure  of 
the  secondary  sexual  characters  (eunuchism).  As 
is  well  known,  the  operation  has  been  practised  for 
centuries  upon  the  attendants  and  guards  of  the 
harem  at  Oriental  courts.  The  beard  and  moustache 
do  not  usually  appear,  the  voice  is  childish,  the  body 
fat,  and  the  mental  attitude  to  the  world  modified, 
although  there  is  no  loss  of  business  capacity.  The 
prostate  and  vesiculae  are  atrophic,  but  there  is  not 
necessarily  impotence.  In  cocks,  testicular  grafting 
partially  obviated  the  effects  of  castration.  Indeed, 
it  is  even  recorded  that  in  a  hen,  after  removal  of  the 
ovaries,  testicular  grafting  caused  the  bird  to  grow 
a  comb,  wattles,  and  spurs,  and  start  to  crow,  but 
this  requires  confirmation. 

Following  upon  Brown-Sequard's  famous  con- 
tention that  feeding  or  injection  of  testicular  extract 
had  made  him  at  72  a  young  man  again,  attempts 


14  THE    GENITAL    GLANDS 

have  been  made,  especially  by  vendors  of  expensive 
patent  remedies,  to  convince  the  profession  that  the 
internal  secretion  of  the  testis  can  be  taken  as  a 
rejuvenating  drug,  recalling  the  classical  story  of 
Medea's  cauldron;  but,  as  Biedl  says,  "exact  and 
carefully  controlled  experiments  with  this  substance 
have  not  been  described."  Auto-suggestion  probably 
accounts  for  much  of  the  alleged  benefit. 

CONTROL  OF  THE  GENITAL  GLANDS  BY 
INTERNAL  SECRETIONS. 

Not  only  are  the  genital  glands  themselves  the 
source  of  internal  secretions,  but  there  is  a  good 
deal  of  accumulating  though  ill-assorted  evidence  to 
show  that  their  own  activity  is  dependent  upon 
chemical  messengers  (hormones),  reaching  them  by 
the  blood-stream,  derived  from  what  we  call  the 
ductless  glands. 

What  is  it  that  makes  a  man  masculine,  and  a 
woman  feminine  ?  It  used  to  be  thought  that  the 
testis  and  the  ovary  were  solely  responsible.  Now 
we  know  that  masculinity  and  femininity  may 
persist  even  after  these  glands  are  removed.  The 
mere  fact  of  infertility  does  not  abolish  sex,  which  is 
dependent  upon  the  combined  working  of  a  num- 
ber of  internal  secretions. 

The    Ductless    Glands   before    Puberty.  —  In 

young  animals  and  in  children  the  development  of 
the  ovary,  testis,  and  other  parts  of  the  genital 
apparatus  depends  upon  chemical  stimuli  received 
from  the  pituitary  and  thyroid  glands.  Experimental 
removal    of    these    glands    in    young    animals,    or 


THE    GENITAL    GLANDS  15 

insufficiency  diseases  of  either  of  them  in  man, 
leads  to  sexual  infantilism. 

On  the  other  hand,  great  enlargement,  and  therefore 
presumably,  hypersecretion  of  the  cortex  of  the 
suprarenal  (hypernephroma),  causes  precocious  sexual 
development  of  the  male  type.  In  boys  this  leads  to 
overgrowth  of  the  sexual  organs  with  early  activity. 
In  girls,  there  is  enlargement  of  the  clitoris,  growth 
of  hair  on  the  face  and  pubes,  and  sometimes  a  male 
type  of  external  genitals  (pseudo-hermaphroditism), 
but  there  is  not  premature  menstruation  or 
fertility. 

Very  few  cases  of  overgrowth  of  the  pineal  gland 
are  on  record,  but  in  some  of  these  there  has  been 
sexual  precocity  in  boys. 

Sexual  precocity  in  girls  is  not  uncommon  ;  it 
appears  to  be  due  to  excessive  ovarian  secretion. 
In  one  case  a  girl  aged  seven  showed  precocious 
development  and  menstruation  ;  an  ovarian  swelling 
was  removed,  and  the  signs  of  puberty  subsided. 

It  is  found  in  gynaecological  practice  that  thyroid 
and  pituitary  feeding  may  hasten  puberty  in  cases 
where  it  is  unduly  delayed.  After  twenty,  how- 
ever, a  small  uterus  cannot  be  stimulated  to  grow. 

We  have  no  sufficient  evidence  yet  of  the  value  or 
otherwise  of  feeding  with  the  ductless  glands  in  cases 
of  crypt  or  chism  with  atrophic  testes. 

The    Ductless    Glands    after    Puberty, — Here 

again  deficient  internal  secretion  of  the  thyroid 
gland  appears  to  be  a  cause  of  amenorrhcea,  painful 
menstruation,  and  monthly  pain  in  the  breasts,  and 
Blair  Bell  statesjthat  thyroid  feeding  cures  many 


16  THE    GENITAL    GLANDS 

such  cases.  It  is  of  course  well  known  that  myx- 
oedema  leads  to  amenorrhcea  and  sterility. 

In  cases  of  pituitary  disorder,  also,  amenorrhcea 
and  sterility  are  the  rule  in  women,  and  impotence 
in  men.  These  are  probably  due  to  deficiency  of 
the  pituitary  secretion,  but  this  is  not  very  clear. 

Not  only  do  the  secretions  of  the  ductless  glands 
influence  the  genital  organs,  but  there  is  evidence  of 
an  effect  in  the  reverse  direction.  During  pregnancy 
the  thyroid  gland  usually  enlarges  a  little  ;  in  Italy 
this  has  been  taken  for  years  as  a  sign  of  conception. 
The  pituitary  gland  also  shows  enlargement  (Erdheim 
and  Stumme).  Berry  points  out  that  adenomatous 
goitre  nearly  always  occurs  in  single  or  nulliparous 
women. 

It  has  already  been  stated  that  removal  of  the 
ovaries  is  a  remedy  for  osteomalacia ;  Bossi  has 
recently  advanced  evidence  that  the  same  effect  may 
be  produced  more  conveniently  by  injections  of 
adrenalin. 

THE     SECRETION     OF     MILK. 

It  is  a  very  striking  phenomenon  that  after  twenty 
or  thirty  years  of  quiescence  the  mammary  glands 
should  suddenly  spring  into  activity  on  the  very  day 
when  the  secretion  is  required.  It  cannot  be  due  to 
nervous  influences,  because  there  is  no  nervous 
mechanism  controlling  the  flow  of  milk.  For  this 
reason  pilocarpine  does  not  increase  and  belladonna 
preparations  do  not  check  the  secretion,  in  spite  of 
their  ancient  reputation  founded  on  analogy.  It  is 
true  that  when  the  child  is  put  to  one  breast  the 


THE    GENITAL    GLANDS  17 

other  may  pour  out  a  little  milk,  but  this  is  due  to 
reflex  contraction  of  the  muscle  about  the  ampullae 
of  the  ducts.  The  only  drug  which  increases  the 
flow  of  milk  is  pituitary  extract,  and  we  have  not 
yet  found  a  way  to  utilize  this  in  the  human  subject. 

The  physiological  stimulus  which  starts  the 
lactation  is  an  internal  secretion  derived  from  the 
fcetus.  Injection  of  extracts  of  foetal  animals  into 
a  non-pregnant  female  of  the  same  species  brings 
about  hypertrophy  and  functional  activity  of  the 
mammary  glands  (Starling  and  Lane-Claypon).  The 
statement  that  this  hormone  is  derived  from  the 
ovary  can  scarcely  be  true,  because  lactation  is 
normal  after  double  oophorectomy.  It  is  not  un- 
common for  the  rudimentary  breasts,  even  of  the 
foetus,  to  be  stimulated  to  a  few  days'  activity 
("  witch's  milk ").  One  of  a  pair  of  conjoined 
Siamese  twins  was  recently  delivered  of  a  child, 
and  both  commenced  lactating. 

Once  started,  the  secretion  of  milk  is  kept  up  by 
suction.  When  this  ceases,  the  glands  return  to  the 
quiescent  state. 

THE     OVUM. 

The  epithelial  and  other  cells  of  the  adult  are  not 
immortal,  and  require  frequent  renewal  to  repair 
daily  wear  and  tear.  The  cell-divisions  bringing 
this  about  are  initiated  by  the  division  of  a  body 
outside  the  nucleus,  called  the  centrosome,  which 
forms  the  achromatic  spindle.  A  skein  appears  in 
the  nucleus,  which  divides  into  V-shaped  bodies 
called  chromosomes,  which  in  man  are  twenty-four 

2 


18  THE    GENITAL    GLANDS 

in  number.  Each  chromosome  splits  into  two,  form- 
ing forty-eight ;  of  these  twenty-four  pass  to  one 
daughter  nucleus  and  twenty-four  to  the  other. 
Finally,  the  cell  protoplasm  cleaves,  and  the  nucleus 
returns  to  its  resting  condition.  This  process  is 
called  homotype  (i.e.  normal)  mitosis. 

Before  it  meets  a  spermatozoon,  the  nucleus  of 
the  ovum  divides  twice,  extruding  the  two  polar 
bodies.  At  the  second  of  these  divisions,*  half  the 
chromosomes — that  is,  in  man,  twelve — are  thrown 
out,  and  the  centrosome  with  them.  This  is  to 
prevent  parthenogenesis  —  the  development  of  an 
ovum  into  a  foetus  without  a  male  element.  In 
bees  and  wasps,  where  parthenogenesis  occurs,  this 
second  or  heterotype  mitosis  does  not  take  place. 

In  the  formation  of  the  spermatozoon,  also,  a 
cell  with  twenty-four  chromosomes  divides  into  two 
spermatozoa  with  twelve  each ;  the  head  is  the 
nucleus,  the  neck  the  centrosome,  and  the  tail  is  the 
cell  body.  Thus  the  foetus  starts  life  with  twenty- 
four  chromosomes,  twelve  from  each  parent.  In 
these,  according  to  Weissmann,  is  bound  up  its 
heredity,  including  the  impulse  to  assume  the  general 
shape  of  mankind,  the  viscera  with  their  proper 
anatomy  and  functions,  and  some  resemblance  to 
the  facial  appearance  and  even  the  tone  of  voice  and 
character  of  the  parents.  How  all  this  is  crowded 
into  such  microscopical  objects  is  the  greatest  marvel 
in  biology. 

The     spermatozoon    probably    brings    in     some 

*  Some  English  text -books  incorrectly  say  the  first. 


THE    GENITAL    GLANDS  19 

chemical  factor,  at  any  rate  in  sea-urchins  and  star- 
fish, because  in  these  animals  the  purely  female  ovum 
can  be  induced  to  develop  into  a  larva  by  concentrated 
seawater,  tannin,  or  even  violent  shaking.  Perhaps, 
however,  these  animals  are  not  far  removed  from 
parthenogenesis,  and  the  part  played  by  the  male 
in  vertebrates  is  probably  more  important. 

After  fertilization,  the  ovum  starts  to  divide  into 
two,  four,  eight,  and  so  on.  Much  light  is  thrown 
upon  the  process  by  the  phenomenon  of  identical 
twins.  Ordinary  twins,  due  to  the  fertilization  of 
two  ova  by  two  spermatozoa,  are  no  more  alike  than 
any  other  pair  of  brothers  or  sisters.  Identical  twins 
probably  result  from  the  accidental  separation  of  the 
two  cells  produced  from  the  first  division  of  a  fertiliz- 
ation ovum,  and  the  children  have  an  identical 
heredity.  They  are  exactly  alike  in  sex,  appearance, 
and  even  in  deformities  such  as  hernia.  This  shows 
that  the  sex  and  general  conformation  of  the  child 
are  probably  fixed  from  the  moment  when  a  particular 
ovum  and  a  particular  spermatozoon  meet. 

CHEMICAL     DIAGNOSIS     OF     PREGNANCY. 

When  an  unusual  protein  passes  repeatedly  into 
the  circulation,  antibodies  of  a  ferment  nature  are 
produced  to  destroy  it.  Some  protein  from  the 
placenta  passes  into  the  maternal  blood-stream 
during  pregnancy.  Abderhalden  has  based  upon 
this  a  method  of  serum  diagnosis.  Fresh  placenta 
is  treated  with  the  patient's  serum,  and  if  she  is 
pregnant  peptones  are  formed  by  digestion.  These 
can  be  dialysed  off  through  an  animal  membrane, 


20  THE    GENITAL    GLANDS 

and  tested  for  by  the  biuret  reaction.  Though 
requiring  extreme  care  in  the  technique,  the  method 
appears  to  be  sufficiently  accurate  and  reliable  to  be 
of  clinical  value. 

REFERENCES. 

Marshall. — "  The  Physiology  of  Reproduction." 
Biedl. — "  The  Internal  Secretory  Organs,"   19 13. 
Blair  Bell. — Proc.  Royal  Soc.  Med.,  1913,    Dec,  vol.  vii, 
Obstetric  section,  p.  47. 


21 


CHAPTER   III. 
SURGICAL     SHOCK. 

The  exhausted  vasomotor  centre  theory  of  Crile  and  Mummery — 
The  acapnia  theory  of  Yandell  Henderson — The  oligaemia  theory 
of  Cobbett  and  Vale — The  adrenalin  exhaustion  theory — The 
nature  of  surgical  shock  ;  its  diagnosis,  treatment,  and  prevention 
— Intravenous  saline  transfusion. 

THERE  were  four  great  barriers  which  stood 
across  the  path  of  the  first  pioneers  of  surgery, 
and  even  to  this  very  day  make  the  quack  and  the 
bonesetter  hesitate  to  resort  to  the  knife.  The  first 
of  these  was  haemorrhage.  The  second  was  pain. 
This  barrier  fell  down  when  anaesthetics  were  intro- 
duced. The  third  was  sepsis,  a  danger  which  Lord 
Lister  showed  us  how  to  triumph  over.  The  last 
great  barrier  to  be  conquered  is  shock.  But  three 
victories  make  us  very  confident  of  final  success, 
and  we  believe  that  one  day  surgery  will  have  lost 
its  main  terrors  and  will  be  able  to  bring  benefit  to 
patients  who  are  now  doomed  to  die  unrelieved  ; 
for  instance,  cases  of  intracranial  or  intrathoracic 
disease,  and  what  we  now  call  inoperable  carcinoma. 
We  may  not  hope  to  prevent  or  treat  surgical  shock 
until  we  have  an  accurate  conception  of  its  nature 
and  causation,  and  we  shall  proceed  to  pass  in  review 
some  of  the  suggestions  which  have  been  made,  and 
to  see  how  they  fare  under  the  criticism  of  exact 
experiment. 


22  SURGICAL    SHOCK 

It  will  be  useful  first  to  quote  from  an  esteemed 
writer  the  symptoms  of  shock  as  they  appeared 
before  attempts  had  been  made  to  fit  them  into 
any  of  the  modern  theories.  Sir  W.  Watson  Cheyne 
wrote  in  1898  :  "  The  patient  who  is  suffering  from 
shock  is  usually  found  lying  in  a  state  of  complete 
muscular  relaxation,  or  if  he  makes  any  movements 
they  are  very  irregular  and  feeble.  The  face  is  pale 
and  drawn,  the  pupils  dilated,  there  is  sweating 
about  the  head,  the  reflexes  are  very  slight,  there  is 
diminished  sensibility,  but  not  absolute  unconscious- 
ness. The  patient  can  answer  questions  when 
spoken  to,  but  if  not  disturbed  will  generally  lie  in  a 
semi-conscious  condition.  The  respirations  are  feeble, 
irregular,  and  sighing.  The  pulse  is  small,  frequent, 
and  dicrotic.  At  first  the  pulse-rate  is  generally 
slowed,  and  increased  frequency  of  the  heart  beat 
is  regarded  by  some  as  a  sign  of  the  commencement 
of  reaction.  The  skin  is  cold  ;  the  temperature 
subnormal."  With  the  possible  exception  of  the 
statements  concerning  the  pulse-frequency,  this 
clinical  picture  will  command  universal  assent.  We 
shall  have  to  refer  to  it  again  later. 

THE   THEORY    OF    CRILE   AND   MUMMERY. 

The  essence  of  the  theory  is  that  the  vasomotor 
centre  in  the  brain  is  first  stimulated  and  then 
exhausted  by  painful,  or  as  we  should  now  say 
nociceptive,  impulses  coming  to  it  from  the  afferent 
nerves.  All  the  phenomena  of  shock  are  due  to 
this  primary  exhaustion  of  the  vasomotor  centre. 
The  most  characteristic   index  of  shock  is  the  fall 


SURGICAL    SHOCK  23 

of  blood-pressure.  It  will  not  be  necessary  here  to 
set  forth  the  arguments  by  which  this  view  was 
defended.  Surgery  undoubtedly  owes  a  great  debt 
to  Crile's  researches.  He  has  established  for  us  the 
importance  of  the  sphygmomanometer  in  measuring 
shock,  the  value  of  nerve-blocking  in  preventing  it, 
and  the  general  principles  of  its  avoidance  and 
treatment.  Nevertheless,  it  is  scarcely  going  too 
far  to  say  that  the  theory  is  beyond  doubt  erroneous. 
It  has  been  maintained  by  a  number  of  competent 
observers,  both  on  clinical  and  experimental  grounds, 
(a)  That  the  peripheral  arteries  may  be  contracted, 
not  dilated,  during  shock  ;  and  (b)  That  the  vaso- 
motor centre  is  not  necessarily  exhausted,  even  in 
extreme  shock.  If  the  failure  of  the  vasomotor 
centre  was  the  main  factor  in  the  genesis  of  shock, 
an  examination  of  the  pulse  and  blood  -  pressure 
would  be  a  sure  indication  of  the  patient's  condition. 
No  doubt  a  bad  pulse  and  a  fall  of  tension  are  grave 
signs,  but  no  surgeon,  anaesthetist,  or  practitioner 
accustomed  to  judge  of  the  prospects  of  a  patient 
after  a  severe  operation  will  dare  to  maintain  that 
because  the  pulse  is  good  and  the  blood-pressure 
normal  there  can  be  no  fear  of  death  from  shock. 
Only  too  commonly,  in  spite  of  an  apparently  efficient 
vasomotor  centre  when  the  patient  leaves  the  table, 
severe  depression  of  all  the  vital  functions  comes  on 
a  few  hours  later,  and  death  follows.  There  may  be 
shock,  then,  with  a  normal  blood-pressure. 

Again,  Mr.  J.  D.  Malcolm  has  repeatedly  pointed 
out  that  the  condition  of  a  patient  in  shock  does 
not  correspond  with  the  clinical  picture  of  vaso- 


24  SURGICAL    SHOCK 

motor  paralysis.  Compare  it,  for  instance,  with 
belladonna  poisoning,  in  which  the  small  arterioles 
are  undoubtedly  released  from  nervous  control, 
causing,  as  we  know,  a  flushed  skin.  In  shock,  on 
the  other  hand,  the  skin  is  pale,  the  pulse  is  small, 
bleeding  is  scanty,  and  the  anuria  suggests  that  the 
renal  vessels  are  contracted.  The  abdominal  viscera 
are  pale  unless  they  have  been  long  exposed.  Seelig 
and  Lyon  point  out  that  the  retinal  blood-vessels 
are  contracted  to  one-half  or  one-third  their  normal 
calibre,  and  amaurosis  may  occur  (it  is  possible, 
however,  that  the  retinal  vessels,  like  the  cerebral, 
are  not  under  the  direct  control  of  the  vasomotor 
system).  Warmth  does  the  patient  more  good  than 
cold,  whereas  if  the  cutaneous  vessels  were  dilated 
the  reverse  should  be  the  case.  Mr.  Malcolm's 
observations  have  not  attracted  the  credence  they 
deserve,  because  it  is  so  difficult  to  understand  how 
there  can  be  a  fall  in  blood-pressure  with  an  efficient 
heart  and  contracted  vessels. 

Animal  experimentation  confirms  the  clinical 
findings.  Even  Professor  Crile  consistently  records 
that  the  arteries  in  shock  are  empty.  He  also  points 
out  that  crushing  the  testes  causes  a  primary  fall 
in  blood-pressure  without  a  previous  rise  ;  the  vaso- 
motor centre,  therefore,  cannot  be  in  a  condition 
of  fatigue  exhaustion.  Seelig  and  Lyon  measured 
the  outflow  from  the  cut  femoral  vein  of  an  animal 
in  five-second  periods.  The  sciatic  nerve  was  then 
cut,  and  the  flow  of  course  increased  in  consequence 
of  the  withdrawal  of  tonic  vasoconstrictor  impulses. 
They   repeated   the    experiment    on    animals    in    a 


SURGICAL    SHOCK  25 

condition  of  extreme  shock.  The  outflow  was 
naturally  less  than  normal,  but  on  cutting  the  sciatic 
nerve  there  was  a  prompt  and  considerable  increase 
in  the  flow.  Therefore  the  vasomotor  centre  must 
still  have  been  sending  out  tonic  impulses.  Again, 
they  found  that  in  normal  animals  stimulation  of  the 
central  end  of  the  cut  vagus  causes  a  rise  in  blood- 
pressure.  The  rise  is  just  as  marked,  in  proportion, 
if  the  experiment  is  repeated  in  an  animal  in  a  state 
of  extreme  shock.  Therefore,  again,  the  centre 
cannot  be  exhausted.  Porter  found  that  the  fall 
of  blood-pressure  due  to  stimulation  of  the  depressor 
nerve  also  takes  place,  and  is  proportionally  as 
marked,  in  shocked  animals.  Tyrrell  Gray  and 
Parsons  found  that  when  an  animal  is  in  a  state  of 
shock  consequent  on  an  operation  on  the  hind  limbs, 
so  that  stimulation  of  the  sciatic  nerve  causes  a  fall 
instead  of  a  rise  of  blood-pressure,  yet  stimulation 
of  the  brachial  nerves  will  still  produce  a  rise.  The 
fatigue,  therefore,  was  in  the  afferent  pressor  paths, 
not  in  the  vasomotor  centre. 

We  are  left,  then,  with  the  conclusion  that  although 
shock  commonly  induces  a  fall  of  blood-pressure, 
the  vasomotor  centre  is  not  primarily  exhausted, 
and  the  vessels  may  be  contracted.  How  can  this 
paradox  be  explained  ?  Boise  believes  that  the 
cause  of  shock  is  spasm  of  the  heart,  but  his  view 
has  met  with  little  favour,  and  his  experimental 
evidence  is  unsatisfactory.  All  observers  agree  that 
the  heart  has  not  seriously  failed  in  shock.  It 
responds  excellently  for  a  time  to  the  extra  work 
put  upon  it  by  a  large  saline  transfusion.     It  is  true 


26  SURGICAL    SHOCK 

that  the  output  of  the  ventricles  in  shock  is  small, 
but  this  is  due  to  deficient  filling,  not  to  impaired 
contractile  power.  Once  again,  then,  we  must  face 
the  crucial  paradox  of  shock,  a  fall  in  blood-pressure, 
in  spite  of  normal  heart  and  contracted  peripheral 
arteries. 

THE  ACAPNIA  THEORY  OF  YANDELL 
HENDERSON. 

During  the  past  few  years  a  most  important,  if 
not  revolutionary,  series  of  papers  has  been  appearing 
in  an  American  journal  of  physiology,  by  Yandell 
Henderson  and  other  workers  in  the  Yale  school, 
dealing  with  surgical  shock  in  animals. 

Because  carbon  dioxide  is  exhaled  from  the  body 
by  the  lungs  ;  because,  in  conditions  of  asphyxia,  the 
amount  of  the  gas  is  greatly  increased  in  the  blood, 
it  has  perhaps  been  too  readily  assumed  that  it  is 
nothing  but  a  poison,  and  serves  no  useful  purpose 
in  the  body  and  in  the  blood.  Haldane  and  Priestley 
showed  several  years  ago,  that  the  activity  of  the 
respiratory  centre  depends,  in  ordinary  circum- 
stances, entirely  on  the  C02  content  of  the  blood. 
When  this  rises  above  a  certain  figure,  constant  for 
the  individual,  respiration  is  stimulated.  This  is  the 
cause  of  each  succeeding  breath  we  draw.  The  gas 
is  being  furnished  to  the  blood  by  the  muscles,  glands, 
and  other  tissues  continuously  ;  each  movement  of 
expiration  reduces  the  blood  content.  In  violent 
exercise  the  breathing  is  excessive  because  more  C02 
is  given  off  by  the  tissues  ;  after  a  swim  under  water 
it  is  excessive  because  the  gas  has  been  accumulating. 


SURGICAL    SHOCK  27 

After  several  voluntary  deep  breaths,  there  is  a 
quiescent  interval,  called  apnoea,  due  to  the  reduction 
of  the  carbon  dioxide  to  such  a  low  figure  that  it  is 
some  time  before  it  reaches  an  amount  sufficient  to 
stir  the  centre  into  activity  again. 

It  will  be  noted  that  it  is  not  lack  of  oxygen  that 
excites  the  respiratory  centre,  but  the  rise  of  the  CO.j 
above  a  certain  percentage.  This  has  been  shown 
not  only  by  blood-gas  analyses  of  the  arterial  and 
venous  blood,  but  also  and  more  especially  by  an 
estimation  of  the  carbon  dioxide  in  the  air  contained 
in  the  alveoli  of  the  lungs.  This  percentage  is  a 
constant  for  the  individual.  In  the  open  air  or  in  a 
crowded  room  the  ventilation  by  the  lungs  is  so 
regulated  as  to  maintain  this  constant.  It  does  not 
vary  in  the  alveoli,  because  it  varies  only  within  the 
narrowest  limits  in  the  blood.  The  amount  of 
oxygen,  on  the  other  hand,  is  by  no  means  constant. 

Now,  so  far,  there  is  no  apparent  application  to 
surgical  shock.  But  Henderson's  thesis  is  that,  not 
only  does  lack  of  carbon  dioxide  induce  apncea,  that 
is,  cessation  of  the  activity  of  the  respiratory  centre, 
but  it  also  reduces  other  important  functions,  so  that 
the  heart  beats  more  quickly  and  the  blood-pressure 
falls.  This  reduction  of  the  C02  is  called  acapnia, 
and  the  suggestion  is  that  acapnia  is  the  prime  cause 
of  shock  {a  =  lack  of ;  capnos  =  smoke). 

According  to  Henderson,  the  deep  and  rapid 
breathing  which,  as  we  all  know,  is  induced  by  pain, 
excitement,  or  exposure  and  handling  of  the  intestines, 
reduces  the  C02  in  the  blood  to  a  very  low  figure, 
whilst  the  oxygen,  of  course,  is  increased.     This  is 


28  SURGICAL    SHOCK 

undeniable,  and  his  blood-gas  analyses  bear  it  out  in 
animals.  Therefore,  when  the  stimulus  ceases, 
breathing  becomes  very  shallow  and  occasional,  and 
at  the  same  time  the  blood-pressure  falls  and  the 
heart  beats  quickly.  This  condition  may  lead  to 
death,  and  indeed  this  is  the  usual  consequence  in 
animals.  Henderson's  theoretical  conclusion  as  to 
the  cause  of  death  is  that  it  is  due  to  lack  of  oxygen, 
the  store  becoming  exhausted  before  the  C02  rises 
high  enough  to  stimulate  the  centre  into  activity 
again ;  but  this  conflicts  with  the  observation  of 
Haldane  and  his  coadjutors,  that  when  the  oxygen 
tension  falls  below  13  per  cent  of  an  atmosphere, 
lack  of  oxygen  assumes  the  power  of  driving  the 
respiratory  centre  whatever  the  C0.2  may  be. 
Perhaps  this  effect  is  due  to  acid  products  thrown 
out  by  the  oxygen-starved  tissues. 

Apart  from  the  dubious  explanation,  however,  the 
facts  merit  careful  attention.  It  is  possible  in 
animals,  merely  by  excessive  artificial  respiration,  to 
reduce  the  C02  so  much  that  respiration  is  shallow, 
the  heart  becomes  rapid,  blood-pressure  falls,  and 
death  ensues  in  about  three  hours.  On  the  other 
hand,  when  the  pulmonary  ventilation  is  reduced, 
and  the  carbon  dioxide  in  the  blood  kept  at  or  near 
its  normal  figure,  very  prolonged  operations  on  dogs, 
extending  over  seven  hours  with  the  thorax  opened, 
result  in  little  or  no  shock.  The  rate  of  heart-beat 
and  the  blood-pressure  can  be  varied  exactly  with 
the  pulmonary  ventilation.  It  is  possible  to  make 
analyses  of  the  blood-gases  with  about  3  ex.  of  blood 
by  Barcroft's  method,  from  time  to  time.     The  means 


SURGICAL    SHOCK  29 

by  which  carbon  dioxide  can  be  restored,  and  shock 
prevented  or  removed,  are :  the  infusion  into  a  vein 
of  saline  saturated  with  C02,  and  the  increase  of  the 
dead  space  of  the  respiratory  apparatus  by  making 
the  animal  breathe  through  a  long  glass  tube,  so 
that  there  is  a  good  deal  of  to-and-fro  breathing  of 
expired  air. 

How  then  are  the  fall  of  blood-pressure  and  the 
quickening  of  the  heart  to  be  explained  ? 

Crile  and  Henderson  agree  that  there  is  no  primary 
cardiac  failure.  After  intravenous  transfusion,  for 
instance,  the  heart  is  perfectly  capable  of  recovery. 
Henderson  finds  the  primary  cause  of  the  failure  in 
the  venous  pressure.  When  there  is  a  reduction  of 
C02  in  the  blood,  the  walls  of  the  veins  and  the 
tissues  supporting  them  relax,  the  pressure  in  the 
veins  falls,  blood  accumulates  in  them,  and  only  a 
small  amount  is  transmitted  to  the  heart.  For  a 
time,  by  constricting  the  arteries,  a  fair  blood-pressure 
can  be  maintained  ;  at  last  the  supplies  reaching  the 
right  auricle  become  so  reduced  that  the  arterial 
pressure  falls,  the  heart-beat  becomes  quick,  the 
output  is  small,  and  severe  shock  is  now  established. 
The  quickened  heart-rate  may  be  due  to  some  extent 
to  escape  from  vagus  control,  the  activity  of  the 
vagus  centre  suffering  reduction,  like  that  of  the 
respiratory  centre,  on  account  of  the  low  blood- 
content  of  carbon  dioxide. 

Some  other  factors  of  importance  require  mention. 
It  is  well  known  that  operations  involving  exposure 
of  the  intestines,  especially  if  they  are  handled  and 
pulled  about,  are  apt  to  induce  shock.     Henderson 


30  SURGICAL    SHOCK 

shows  that  when  the  abdominal  viscera  are  exposed 
to  a  current  of  air,  they  rapidly  exhale  COa.  The 
rate  of  loss  is  about  forty  times  as  great  as  that  from 
the  skin.  Consequently  there  is  both  a  local  and 
a  general  reduction  of  the  carbon  dioxide.  The 
vessels  of  the  peritoneum  become  dilated,  peristalsis 
is  reduced  or  inhibited  altogether,  and  the  systemic 
lack  of  C02  results  in  apncea  and,  finally,  the  vascular 
phenomena  of  shock.  It  is  well  known  that  in 
partial  asphyxia  the  intestinal  movements  are 
exaggerated.  If  the  peritoneal  cavity  is  filled  with 
C02  gas,  peristalsis  is  very  active,  like  that  seen  with 
the  #-rays  in  a  normal  animal,  and  quite  unlike  the 
quiescence  which  we  are  accustomed  to  observe  even 
under  light  anaesthesia.  Saline  fluid  saturated  with 
C02  also  produces  peristalsis,  avoids  that  paralytic 
condition  of  the  bowel  which  is  a  bugbear  of 
abdominal  surgery,  and  prevents  the  redness  and 
congestion  of  the  vessels  induced  by  the  local  acapnia. 
Whilst  the  handling  and  pulling  are  actually  going 
on,  the  painful  stimuli  are  sufficient  to  avert  fatal 
respiratory  failure.  It  is  well  known  that  any  pain 
increases  the  rate  and  depth  of  breathing.  If  death 
from  shock  occurs  at  this  stage,  it  will  be  by  failure 
of  the  circulation.  But  as  soon  as  the  painful  im- 
pulses cease,  neither  pain  nor  COa  is  present  to  stir 
the  respiratory  centre  into  activity,  and  death  by 
failure  of  respiration  soon  ensues.  It  is  a  common- 
place that  patients  usually  survive  the  operation 
itself,  but  may  die  of  shock  a  few  hours  afterwards. 
Henderson  found  that  even  a  few  minutes'  cessation 
of  the  stimuli  would  allow  the  animals  to  lapse  into 


SURGICAL    SHOCK  31 

his  fatal  apnoea,  while  breathing  could  be  restored 
on  resuming  the  handling. 

Deficiency  of  C0.2  in  the  blood  has  another  remark- 
able effect.  When  the  deviation  from  normal  is 
considerable,  there  is  a  tendency  for  fluid  to  exude 
from  the  plasma  into  the  tissues  with  great  rapidity. 
This  was  first  demonstrated  by  Sherrington  and 
Copeman.  The  plasma  therefore  becomes  con- 
centrated, and  the  total  volume  of  the  blood  is 
diminished.  This  further  reduces  the  output  of  the 
heart.  When  this  outpouring  has  become  established, 
transfusion  ceases  to  be  of  more  than  temporary 
benefit.  Early  in  the  course  of  shock,  the  intro- 
duction of  saline  into  a  vein  will  cure ;  later  on  it 
fails  because  the  fluid  merely  escapes  into  the 
tissues. 

Shock,  or  a  condition  exactly  analogous  to  shock, 
may  be  induced  not  only  by  injury  or  pain,  but  also 
by  toxaemia.  Whilst  Crile  was  investigating  the 
former  condition,  Romberg  and  Passler  were  making 
observations  on  the  latter.  They  found  that  tox- 
emic shock  was  identical  in  its  main  features  with 
traumatic  shock,  and,  like  Crile,  they  considered 
that  it  was  due  not  to  heart  failure  but  to  exhaustion 
of  the  vasomotor  centre  after  prolonged  activity. 
According  to  Henderson,  however,  in  both  these 
conditions  it  is  the  venous  pressure  and  the  venous 
return  to  the  heart  which  are  subnormal  in  the  first 
place,  and  the  final  fall  in  the  arterial  pressure  is  due 
not  to  exhaustion  of  the  vasomotor  centre,  but  to 
the  reduced  output  of  the  heart ;  this  reduced  out- 
put, in  its  turn,  being  due  not  to  cardiac  weakness  but 


32  SURGICAL    SHOCK 

to  inadequate  entry  of  blood  along  the  venae  cavae. 
Both  Crile  and  the  German  observers  laid  great  stress 
on  the  fact  that  stimulation  of  a  sensory  nerve  fails 
to  induce  the  usual  rise  of  blood-pressure,  by  reflex 
arterial  constriction,  when  advanced  shock  is  present, 
and  they  interpreted  this  as  due  to  exhaustion  of  the 
vasomotor  centre ;  according  to  Henderson,  the 
truth  is  that  the  centre  is  already  sending  out  its 
maximum  of  impulses,  but  that  the  pressure  is  low 
notwithstanding,  because  there  is  so  little  blood 
actually  circulating.  He  remarks  that  if  the  arteries 
were  paralysed,  an  intravenous  injection  of  saline 
would  not  raise,  as  it  frequently  does,  the  arterial 
blood-pressure  to  normal,  "  because  the  blood  would 
run  out  through  the  capillaries  too  easily  for  any 
pressure  to  be  developed." 

There  is  experimental  evidence  that  the  venous 
pressure  is  not  regulated  by  the  nervous  system,  but 
rises  and  falls  with  the  amount  of  C0.2  in  the  blood. 
Adrenalin  has  no  influence  on  it.  The  carbon  di- 
oxide acts  partly  by  influencing  the  tone  of  the 
muscle  in  the  vein  wall  and  in  the  supporting 
external  tissues,  and  partly  by  controlling  the  escape 
of  fluid  by  osmosis. 

The  measures  which  he  used  to  prevent  shock 
were  to  diminish  the  loss  of  carbon  dioxide  by  keep- 
ing the  artificial  respiration  very  slow,  and  using  a 
long  tube  attached  to  the  trachea,  so  that  a  good 
deal  of  the  expired  air  was  in-breathed  again.  To 
relieve  shock  he  adopted  three  measures  : — 

i.  Pouring  warm  saline  saturated  and  bubbling 
with  C02  into  the  abdomen,  and  closing  the  cavity. 


SURGICAL    SHOCK  33 

2.  Transfusing  warm  saline  saturated  and  bubbling 
with  C0.2  into  a  vein. 

3.  Allowing  the  animal  to  breathe  in  and  out  of  a 
bag  containing  air  or,  better,  oxygen. 

The  saline  is  saturated  by  shaking  it  in  a  flask 
through  which  carbon  dioxide  has  been  bubbled  from 
a  cylinder  or  Kipp's  apparatus  ;  it  is  then  warmed. 
The  delivery  tube  from  the  C02  cylinder  may  be 
introduced  into  the  abdominal  cavity,  and  the  gas 
bubbled  through  the  fluid. 

We  may  sum  up  the  sequence,  then,  as  follows  : — 

1.  Hyperpncea,  that  is,  excessive  breathing  due  to 
painful  or  nociceptive  impulses. 

2.  Leading  to  acapnia,  that  is,  reduction  of  carbon 
dioxide  in  the  blood.  In  abdominal  operations 
carbon  dioxide  is  exhaled  from  the  intestines,  giving 
rise  to  a  further  reduction. 

3.  Acapnia  causes  failure  of  the  veno-pressor 
mechanism,  that  is,  loss  of  tone  and  consequent 
dilatation  of  the  veins.  According  to  the  author, 
venous  tone  is  controlled  by  the  C02  in  the  blood. 

4.  Venous  anoxhcemia,  tissue  asphyxia,  acidosis. — 
Owing  to  the  reduction  of  C02  in  the  blood,  the 
respiratory  centre  is  not  roused  to  activity,  and  the 
oxygen  in  the  blood  is  therefore  not  renewed,  so 
that  the  tissues  suffer  from  deprivation  of  oxygen, 
and  acid  products  enter  the  blood. 

5.  Acute  oligcemia, — Henderson  considers  that  loss 
of  carbon  dioxide  leads  in  some  obscure  way  to 
rapid  escape  of  the  plasma  from  the  circulatory 
blood  out  into  the  tissues. 

6.  Death,  usually  from  tissue  asphyxia,  or  from 

3 


34  SURGICAL    SHOCK 

failure  of  enough  blood  to  get  back  to  the  heart  to 
continue  the  circulation,  on  account  of  the  oligaemia 
and  the  dilated  toneless  veins. 

Whilst  fully  recognizing  the  great  value  of  this 
research,  the  labour  expended  upon  it,  and  the 
learning  with  which  it  has  been  supported,  the 
present  writer,  although  at  first  attracted  by  the 
theory,  has  felt  compelled  to  abandon  it  as  an 
explanation  of  routine  surgical  shock  in  man.  No 
doubt  it  is  possible  to  induce  a  condition  resembling 
shock  by  acapnia  in  animals,  and  probably  in  man, 
and  enthusiastic  anaesthetists  who  are  experimenting 
with  the  intratracheal  administration  of  ether  will 
do  well  to  study  Yandell  Henderson's  original  papers. 

The  objections  to  acapnia  as  an  explanation  of 
human  surgical  shock  following  injury  or  operation 
are  as  follows.  Some  purely  physiological  criticisms 
are  omitted,  (i)  Hyperpncea  from  painful  stimuli 
is  not  sufficiently  severe  or  prolonged,  one  would 
have  thought,  to  reduce  the  C0.2  from  40  to  50  per 
cent,  the  normal,  down  to  10  per  cent,  as  in  some 
of  Henderson's  analyses  of  the  blood  in  shocked 
animals.  Shock  often  comes  on  quite  soon,  in  half 
an  hour  or  less.  (2)  If  the  theory  were  true,  shock 
would  be  impossible  during  an  operation  where  a 
Clover's  inhaler  was  used  throughout.  Some  anaes- 
thetists believe  that  the  Clover  is  better  than  open 
ether  in  averting  shock,  but  no  one  will  suggest 
that  any  operation,  however  severe,  can  be  performed 
with  safety  provided  the  patient  is  kept  blue. 
(3)  Even  in  animals  in  a  condition  of  acapnia  it 
was  not  found  possible  to  save  their  lives  by  carbon 


SURGICAL    SHOCK  35 

dioxide.  (4)  All  Henderson's  work  was  upon  animals 
under  experimental  conditions.  It  is  quite  unsafe 
to  apply  the  results  to  human  surgery  without 
study  of  the  C0.2  content  of  the  blood  in  man. 
The  writer  has  therefore  made  analyses  of  the 
blood  of  patients  and  normal  persons  by  means  of 
Barcroft's  apparatus.  A  hypodermic  syringeful  of 
blood  was  withdrawn  from  the  median  basilic  or 
other  vein,  and  the  C02  content  estimated  immedi- 
ately. It  was  found  that  in  five  patients  showing 
shock,  three  of  whom  died,  the  quantity  of  carbon 
dioxide  present  was  about  46*9  per  cent,  that  is, 
a  fraction  higher  than  the  normal.  In  Yandell 
Henderson's  observations  the  C02  fell  to  10  or  20 
per  cent.  Two  patients  with  cyanosis  showed  a 
rise  to  59*5  and  74^2  per  cent,  proving  that  the 
method  of  estimation  was  capable  of  detecting  the 
variations.  Janeway  and  Ewing  have  recently 
published  the  results  of  some  animal  experiments 
showing  that  excessive  artificial  respiration  will 
induce  shock  even  if  the  C02  content  of  the  blood 
is  kept  high. 

We  conclude,  therefore,  that  acapnia  is  not  the 
cause  of  ordinary  surgical  shock.  We  are  still  left 
face  to  face  with  the  problem  of  a  falling  blood- 
pressure  with  normal  heart  and  contracted  arteries. 

THE     OLIGEMIA     THEORY     OF     COBBETT 
AND     VALE. 

There  is  one  very  tempting  explanation  of  the 
phenomena  of  shock  to  which  attention  must  next 
be  directed.     If  the  total  blood  volume  were  reduced 


36  SURGICAL    SHOCK 

(oligcemia  =  scanty  blood)  the  blood-pressure  would 
fall  and  yet  the  heart  and  vasomotor  centre  might 
act  well  and  the  arteries  be  constricted.  Sherring- 
ton and  Copeman  have  shown  that  intraperitoneal 
operations  and  also  scalds  in  animals  do,  as  a  matter 
of  fact,  raise  the  specific  gravity  of  the  blood.  An 
intestinal  anastomosis  lasting  a  quarter  of  an  hour 
raised  the  specific  gravity  in  one  animal  from  1*054 
to  1*062. 

Roy  and  Cobbett  opened  the  abdomen  in  dogs 
and  cut,  pulled,  or  ligatured  the  intestines  for  12  to  18 
hours  continuously  under  an  anaesthetic.  At  first 
the  blood  showed  no  change,  then  its  specific  gravity 
rose  steadily,  as  much  as  by  0*014  a^  the  end  of  the 
prolonged  manipulations.  The  specific  gravity  of 
the  intestines  fell  ;  that  of  the  muscles  rose.  The 
blood-pressure  began  to  drop  some  hours  after  the 
specific  gravity  of  the  blood  rose.  Cobbett  has 
published  these  researches  with  the  suggestion  that 
a  similar  concentration  of  the  blood  is  the  causative 
factor  in  surgical  shock,  and  Vale  has  attempted  to 
establish  the  theory  by  blood  examinations  in  man. 
On  this  view  shock  and  collapse  are  identical.  The 
suggestion  is,  of  course,  that  the  fluid  lost  has  been 
poured  out  into  the  injured  area.  Griinbaum  is 
quoted  by  Cobbett  as  having  examined  the  blood 
after  three  laparotomies  in  man,  and  in  each  case 
there  was  a  rise  of  from  5  to  7  points,  but  no  details 
are  given.  Vale  made  observations  on  four  patients, 
estimating  the  specific  gravity  by  the  Roy  method. 
In  the  first  case  an  abdominal  fistula  was  closed  by 
operation  ;   the  specific  gravity  before  operation  was 


SURGICAL    SHOCK  37 

1-053,  and  afterwards  1-063  '>  there  is  said  to  have 
been  "  mild  shock,"  but  the  blood-pressure  was 
130.  Three  other  cases  were  accidents  each  showing 
"  mild  shock."  The  results  were  as  follows  :  Case 
2,  when  seen,  specific  gravity  1-063,  next  day  1*058. 
Case  3,  when  seen,  specific  gravity  1-066,  next  day 
1-064.  Case  4f  when  seen,  specific  gravity  1-063. 
next  day  1-058.  Although  one  is  attracted  by  this 
theory  at  first  sight,  and  it  has  been  accepted  by 
Malcolm  and  Yandell  Henderson,  it  is  difficult  to 
understand  where  all  the  fluid  has  escaped  to, 
or  what  drives  it  out.  One  does  not  see  much 
exudate,  for  instance,  in  an  amputation  at  the  hip- 
joint,  but  shock  may  be  severe.  Vale's  analyses 
were  made  by  the  difficult  Roy  method,  and  although 
his  figures  appear  higher  than  usual,  this  is  due  to 
the  fact  that  those  ordinarily  quoted  are  obtained 
by  Hammerschlag's  method,  which  gives  results 
decidedly  lower.  Moreover,  it  does  not  appear  that 
any  of  Vale's  cases  were  suffering  from  a  marked 
degree  of  shock.  However,  it  was  not  difficult  to 
obtain  definite  evidence  as  to  the  correctness  of  the 
theory,  and  I  have  therefore  estimated  the  specific 
gravity  of  the  blood  in  a  number  of  cases  of  surgical 
shock. 

Method. — Hammerschlag's  method,  slightly  modi- 
field,  was  employed.  A  mixture  of  chloroform  and 
xylol  was  prepared  having  a  specific  gravity  approxi- 
mately that  of  blood.  A  few  drops  of  blood  were 
obtained  from  the  patient's  ear,  without  squeezing, 
and  immediately  transferred  by  a  capillary  tube  to 
the   mixture,    to   which   chloroform   or   xylol   were 


38  SURGICAL    SHOCK 

added  until  the  blood  neither  rose  nor  sank.  The 
whole  estimation  needs  to  be  carried  out  quickly. 
Then  the  specific  gravity  of  the  mixture  was  taken 
with  a  hydrometer.  It  is  easy  to  obtain  readings 
correct  to  the  third  decimal.  As  Levy  has  pointed 
out,  the  method  gives  results  which  are  rather  too 
low,  because  the  hydrometer  is  graduated  for  watery 
solutions,  and  surface  tension  in  the  chloroform- 
xylol  mixture  is  different.  One  has  therefore  to 
use  the  same  hydrometer  and  correct  its  readings  by 
a  special  estimation.  With  the  hydrometer  used 
in  these  experiments  one  has  to  add  0-003  to  the 
reading  obtained.  The  normal  specific  gravity  of 
human  blood  is  about  1-057  i*1  women  and  1-060 
in  man.  These  results  are  rather  higher  than  those 
quoted  by  the  older  text -books,  because  these  did 
not  correct  the  hydrometer  readings.  All  the  figures 
given  here  are  corrected  readings.  Out  of  a  large 
number  of  analyses  made  on  patients  under  the  care 
of  various  surgeons  at  the  Bristol  Royal  Infirmary, 
it  was  found  that  there  was  never  a  marked  rise  of 
specific  gravity  in  ordinary  surgical  shock.  In  all 
but  one  case,  there  was  practically  no  rise,  and 
several  times  there  wa,  a  fall.  Therefore  oligaemia 
cannot  be  an  important  factor  in  shock.  Three 
typical  analyses  are  given  here  as  illustrations. 

I.  Female,  aged  4j.  Wertheim's  hysterectomy 
for  cancer  of  cervix.  Fall  anoci-association.  Bladder 
wounded  and  sewn  up.  Bad  shock  at  end  (two 
hours),  pulse  quick  and  feeble,  blood-pressure  70. 
At  beginning,  specific  gravity,  1-046  ;  at  end,  specific 
gravity,  1-047.     Sequel,  died  fifteen  hours  after. 


SURGICAL    SHOCK  39 

2.  Male,  aged  40.  Arthroplasty  of  hip  ;  patient 
feeble,  with  ankylosed  spine.  Took  one  and  a  half 
hours.  Pulse  soft  and  feeble,  disappeared  at  intervals. 
Blood-pressure  near  end,  85  ;  temperature  after 
operation,  96-6°.  Specific  gravity  at  beginning,  1-062. 
Specific  gravity  at  end,  1-063.  Sequel,  recovered. 
Blood-pressure  three  days  later,  115. 

3.  Female,  aged  18.  Extensive  burns  seven  hours 
before,  involving  abdomen,  buttocks,  thighs,  hands, 
and  arms.  Pulse  good,  but  looked  ill ;  vomiting  ; 
thirsty.  Specific  gravity,  1-072.  Next  day,  specific 
gravity,  1-072.  Twelve  days  later  specific  gravity, 
1-059.     Sequel,  recovered. 

It  will  be  observed  that  Cases  1  and  2  showed 
every  sign  of  grave  shock,  but  there  was  no  con- 
siderable alteration  of  specific  gravity  ;  nothing  but 
a  rise  of  o-oio  would  influence  blood-pressure. 

In  Case  3  and  in  other  burn  cases,  however,  there 
was  a  very  remarkable  rise,  corresponding  to  a  loss 
of  fluid  of  about  one  quart,  and  lasting  over  twenty- 
four  hours.  Probably  this  is  the  cause  of  some  of 
the  symptoms  of  a  severe  burn,  and  obviously  the 
administration  of  saline  is  urgently  indicated. 

A  third  point  of  interest  is  with  reference  to  two 
cases  of  Wertheim's  hysterectomy.  It  was  observed 
that  the  specific  gravity  before  operation  was  very 
low — 1-048  and  1-046,  instead  of  1-057.  This  was 
probably  the  result  of  prolonged  loss  of  blood.  Both 
cases  died  from  shock.  It  has  been  found  by  Douglas 
that  a  fall  in  the  specific  gravity  of  the  blood  is 
common  in  cancerous  cachexia.  We  may  have  here 
an   easy   means   of   detecting   cases  whose   general 


40  SURGICAL    SHOCK 

condition  is  already  too  grave  to  permit  of  major 
surgery.  The  estimation  of  the  specific  gravity  is 
simple,  only  takes  three  minutes,  and  can  be  done 
with  a  drop  or  two  of  blood.  It  remains  to  be 
determined  just  where  the  limits  of  safety  lie.  In 
the  two  fatal  cases  there  was  a  fall  of  o-oio. 

THE   SUPRARENAL   EXHAUSTION  THEORY. 

Perhaps  no  one  has  definitely  formulated  any 
such  theory  as  yet,  but  it  is  certainly  deserving  of 
examination.  Recent  physiological  research  has 
shown  that  painful  stimuli  lead  to  a  reflex  outpouring 
of  adrenalin  from  the  suprarenal  glands  into  the 
circulating  blood.  If  this  took  place  to  a  considerable 
extent  there  would  be  a  preliminary  rise  of  blood- 
pressure,  followed,  perhaps,  by  suprarenal  exhaustion 
and  a  profound  fall  of  pressure  in  spite  of  a  normal 
heart  and  vasomotor  centre.  Bainbridge  and  Parkin- 
son found  absence  of  the  chromaffin  substance  in  the 
medulla  of  the  suprarenals  in  two  patients  who  died 
from  shock.  Priestley  found  the  same  absence  in 
84  per  cent  of  cases  dying  with  a  low  blood-pressure. 
Here,  at  least,  is  a  prima  facie  case  for  the  supra- 
renal exhaustion  theory. 

Examination  of  the  chromaffin  substance  is  not 
a  very  convincing  means  of  settling  the  problem. 
It  is  quite  probable  that  the  chromaffin  substance 
and  the  adrenalin  content  run  parallel,  and  there 
are  observations  in  support  of  this  view,  but  it  would 
be  much  more  satisfactory  to  make  direct  estimations 
of  the  quantity  of  adrenalin  in  the  blood  and  in  the 
suprarenal  glands  in  cases  of  shock.     For  this  purpose 


SURGICAL    SHOCK  41 

I  have  devised  an  adrenalino scope,  which  is  a  further 
advance  on  a  method  already  used  by  Douglas  Cow 
and  also  by  O.  B.  Meyer. 

THE     AUTHOR'S     ADRENALINOSCOPE. 

A  rabbit  is  killed  by  a  blow  on  the  head,  and  the 
thoracic  aorta  rapidly  dissected  out.  With  fine 
sharp  scissors  a  spiral  strip  of  aorta  is  cut  about  a 
quarter  of  an  inch  wide  from  the  whole  length  of 
the  aorta.  We  thus  obtain  a  strip  about  three 
inches  long,  in  which  the  circular  muscle  of  the  aorta 
is  running  longitudinally,  so  that  a  vasoconstrictor 
drug  will  induce  shortening.  One  end  of  the  spiral 
is  transfixed  on  a  hook  secured  in  a  cork  at  the 
bottom  of  a  vertical  glass  cylinder,  and  the  upper 
end  is  connected  by  a  thread  with  a  long  lever 
recording  its  movements  on  a  smoked  drum.  The 
spiral  is,  of  course,  stretched  straight  by  the  weight 
of  the  lever.  The  glass  cylinder  contains  warm 
normal  saline,  which  can  be  drawn  off  through  a 
tube  with  stopcock  in  the  cork  at  the  bottom,  and 
replaced  by  running  in  the  test  fluid  gently  down 
the  side  of  the  cylinder  containing  the  strip  of  aorta. 
If  any  appreciable  quantity  of  adrenalin  is  present, 
the  distant  point  of  the  writing  lever  will  rise  within 
a  minute  or  two,  and  then  fall  again  a  few  minutes 
later.  It  is  difficult  to  avoid  a  very  steady  fall  of 
the  point  of  the  lever  from  stretching  of  the  aorta, 
but  this  does  not  interfere  with  the  reaction. 

This  adrenalinoscope  is  extraordinarily  delicate, 
and  will  show  an  appreciable  contraction  with  as 
little  as  i  in  500  million  of  Parke,  Davis  &  Co.'s 


42  SURGICAL    SHOCK 

adrenalin  (i.e.,  I  in  500,000  of  their  solution,  which 
is  1  in  1000).  I  have  used  this  method,  first,  to 
find  whether  there  is  any  evidence  that  the  blood 
is  flooded  with  adrenalin  during  a  surgical  operation  ; 
and  second,  to  estimate  the  relative  quantity  of 
adrenalin  left  in  the  suprarenal  glands  after  death 
from  shock.  In  two  cases  a  hypodermic  syringeful 
of  oxalated  blood  was  withdrawn  from  a  vein  towards 
the  end  of  the  operation,  and  diluted  with  sufficient 
saline  to  fill  the  glass  cylinder  containing  the  spiral 
strip.  In  neither  case  was  any  adrenalin  contraction 
recorded. 

It  may  be  objected  that  there  would  not  be  suffi- 
cient adrenalin  in  the  circulating  blood  of  the  patient 
to  react  even  to  so  delicate  an  adrenalinoscope  as 
one  detecting  1  in  500  million,  but  calculating  from 
the  supposed  quantity  in  the  human  suprarenals, 
5  mgrams  according  to  Battelli,  it  is  difficult  to 
believe  that  the  glands  could  be  exhausted  in  an 
hour  or  two  and  yet  the  amount  in  the  blood  escape 
recognition. 

More  convincing,  perhaps,  are  observations  on 
the  suprarenal  glands  of  patients  dying  from  shock. 
These  were  removed  as  soon  as  possible  after  death 
(from  six  to  twenty-four  hours),  packed  and  trans- 
ported in  ice,  cut  open  in  15  c.c.  of  normal  saline, 
and  the  medullas  thoroughly  scraped  out.  Various 
dilutions  in  normal  saline  were  then  tested  in  the 
adrenalinoscope  to  determine  the  highest  dilution 
giving  a  definite  rise  of  the  lever.  In  four  cases  of 
shock,  tested  against  controls,  there  was  no  reduction 
of  adrenalin  in  the  suprarenals.     In  fact,  the  patient 


SURGICAL    SHOCK  43 

showing  the  largest  quantity  of  adrenalin  was  a 
woman  who  died  as  the  result  of  a  street  accident 
producing  multiple  fractures  and  leading  to  a  fatal 
issue  in  four  and  a  half  hours.  Adrenalin  exhaustion, 
therefore,  is  not  the  cause  of  surgical  shock. 

WHAT,   THEN,   IS     THE    NATURE   OF   SURGICAL 

SHOCK? 

We  have  failed  to  discover  any  evidence  that 
changes  in  the  blood  are  the  essential  factor  in  the 
production  of  surgical  shock,  and  are  left  face  to  face 
again  with  the  crucial  problem,  how  to  find  an 
explanation  for  a  falling  blood-pressure  with  a  normal 
heart  and  vasomotor  centre  and  contracted  peri- 
pheral arteries.  Since  the  examination  of  the  blood 
has  not  helped  us,  we  must  return  to  the  central 
nervous  system. 

There  is  a  condition  well  known  to  experimental 
physiologists  called  spinal  shock.  In  monkeys,  and 
to  a  much  less  extent  in  cats  and  dogs,  a  high  tran- 
section of  the  spinal  cord  is  followed  by  grave 
interference  with  the  functions  of  the  cord  distal 
to  the  section.  For  a  period  varying  from  hours  to 
days  no  reflexes  can  be  obtained,  muscular  tone  is 
abolished,  and  the  peripheral  blood-vessels  dilate. 
In  human  surgery  we  see  the  like  condition  in  spinal 
concussion,  in  which,  after  a  blow  on  the  back, 
sensation,  voluntary  power  of  movement,  and  reflexes 
may  be  abolished,  but  after  a  day  or  two  are  all 
restored  to  normal. 

Professor  Sherrington  has  made  some  important 
investigations  into  the  nature  of  spinal  shock.     In 


44  SURGICAL    SHOCK 

the  first  place,  he  shows  that  it  only  affects  those 
segments  of  the  cord  distal  to  the  lesion  ;  thus,  after 
an  upper  dorsal  transection  the  cervical  segments 
are  not  in  shock.  Secondly,  he  shows  that  after 
recovery  has  taken  place,  a  second  transection — for 
instance,  in  the  mid-dorsal  region — will  not  repro- 
duce the  signs  of  spinal  shock,  proving  that  it  was 
due  to  the  withdrawal  of  influences  descending 
from  the  brain  or  brain  stem.  Again,  cutting  across 
the  mesencephalon,  above  the  pons,  does  not  in- 
duce spinal  shock.  Therefore  the  impulses  pre- 
venting it  must  have  come  down  from  the  region 
of  the  fourth  ventricle.  We  also  know  that  from 
this  same  region,  and  in  particular  from  the  central 
nuclei  of  the  vestibular  nerve,  descend  the  impulses 
which  give  rise  to  excess  of  muscular  tone.  A 
transection  of  the  mid-brain  causes  decerebrate 
rigidity  of  the  limbs  ;  a  second  transection  below 
the  medulla  abolishes  the  excess  of  tone.  On  this 
subject  the  writings  of  Sherrington  and  of  Thiele 
may  be  consulted. 

F.  H.  Pike,  of  Columbia  University,  has  lately 
published  a  vety  important  research  on  spinal  shock 
with  particular  reference  to  the  blood-pressure.  He 
shows  that  there  is  a  certain  residual  blood-pressure, 
about  33  mm.  of  mercury,  even  after  removal  of  the 
brain,  provided  that  the  cord  is  left  intact,  and  that 
sensory  stimuli  will  raise  this  pressure  reflexly. 
When  the  cord  is  totally  removed  there  is  a  very 
great  fall  of  pressure.  Apart  from  removal  of  the 
cord,  curare  produces  a  considerable  reduction  of 
blood-pressure,  both  in  normal  and  in  spinal  animals. 


SURGICAL    SHOCK  45 

This  curare  effect  is  not  due  to  any  action  on  the 
vessels,  but  to  the  abolition  of  tone  of  the  voluntary 
muscles.  This  is  in  accord  with  the  results  of  other 
workers. 

Do  we  not  here  find  a  clue  to  our  problem  ?  We 
turn  back  to  the  very  first  sentence  of  Sir  Watson 
Cheyne's  classical  description  of  shock,  and  read, 
"  The  patient  who  is  suffering  from  shock  is  usually 
found  lying  in  a  state  of  complete  muscular  relaxa- 
tion." And,  later,  "  the  reflexes  are  very  slight. " 
Loss  of  tone  in  the  voluntary  muscles,  in  the  abdominal 
wall  especially,  allows  great  dilatation  of  the  veins, 
and  here,  as  Crile  observed  in  his  experimental 
animals,  the  blood  accumulates.  Therefore  the 
blood-pressure  falls  and  the  cardiac  output  is  reduced 
in  spite  of  undiminished  power  of  the  heart  muscle 
and  contracted  arteries. 

We  must  draw  attention  to  the  very  significant 
fact  that  although  the  intramuscular  and  abdominal 
veins  are  dilated  in  shock,  this  cannot  be  due  to 
some  universal  venodilator  effect,  because,  as  anyone 
who  has  had  to  perform  intravenous  transfusion 
on  these  cases  will  bear  witness,  the  subcutaneous 
veins  are  smaller  than  normal.  It  may  be  objected 
that  muscular  tone  is  reduced  in  various  nervous 
diseases  and  under  anaesthetics  without  a  marked 
fall  of  blood-pressure,  but  it  has  to  be  remembered 
that  in  the  nervous  affections  the  onset  is  very 
gradual  and  can  be  compensated,  and  with  anaesthetics 
there  is  stimulation  of  the  heart  and  vasomotor 
centre  to  counteract  the  loss  of  tone.  Under  ether, 
at  any  rate,  the  muscles  may  be  very  vigorous,  as 


46  SURGICAL    SHOCK 

rigidity  of  the  abdominal  wall  frequently  reminds  us. 
Chloroform,  of  course,  does  reduce  the  blood-pressure 
after  a  time. 

Without  venturing  to  formulate  a  cut-and-dried 
theory,  then,  one  may  suggest  that  the  nociceptive 
impulses  which  bring  about  surgical  shock  do  so  by 
inhibiting  or  paralyzing  the  important  nuclei  in  the 
region  of  the  fourth  ventricle  and  perhaps  in  the 
cerebellum,  which,  as  Sherrington  and  others  have 
shown,  are  continually  sending  impulses  down  the 
spinal  cord,  maintaining  its  functional  activity  and 
increasing  muscular  tone.  When  such  inhibition 
or  paralysis  takes  place  the  functions  of  the  cord 
are  greatly  reduced,  tone  is  abolished,  and  there- 
fore, as  a  secondary  result,  the  blood-pressure  may 
fall.  The  respiratory  centre,  and  perhaps  even  the 
vasomotor  centre,  share  in  this  inhibition  or 
paralysis  ;  this  is  a  very  different  conception  from 
that  which  takes  exhaustion  of  the  vasomotor 
centre  to  be  the  prime  cause  of  all  the  symptoms. 
Death  is  due  to  accumulation  of  blood  in  the  great 
veins,  so  that  the  vis  a  tergo  is  no  longer  able  to 
provide  a  proper  filling  for  the  heart,  especially  as 
the  feeble  respiratory  movements  fail  to  exert  their 
important  pumping  action. 

A  very  striking  example  of  this  sequence  is  met 
with  in  what  is  called  "  the  knock-out  blow  "  in 
pugilism,  or  rather,  one  of  such  blows.  A  vigorous 
drive  on  the  point  of  the  lower  jaw  in  a  line  from 
the  chin  to  the  condyles  is  transmitted  directly  to 
the  labyrinth  of  the  internal  ear,  and  by  way  of  the 
vestibular  nerve  impulses  reach  the  nuclei  of  which 


SURGICAL    SHOCK  47 

we  have  been  speaking.  As  a  result  a  powerful 
athlete  is  immediately  reduced  to  a  mass  of  quivering, 
unstrung  flesh,  and  may  die  outright.  In  a  word, 
he  is  in  a  state  of  shock. 

Perhaps  it  may  be  found  possible  to  localize  with 
accuracy  the  nuclei  which  are  principally  affected 
in  surgical  shock  by  histological  examination  for 
chromatolysis.  Dolley  and  Crile  have  published 
very  remarkable  observations  on  changes  in  the 
nerve-cells  in  shocked  or  hunted  animals,  showing 
dissipation  of  the  Nissl  granules.  These  changes 
were  best  marked,  not  in  the  vasomotor  centre  as 
Crile's  theory  would  demand,  but  in  the  Purkinje 
cells  of  the  cerebellum.  Tyrrell  Gray  and  Parsons 
found  changes  in  the"  cuneate  and  gracile  nuclei  of 
the  medulla. 

I  have  so  far  had  the  opportunity  of  examining 
the  brain  of  only  one  case  by  this  laborious  method, 
and  therefore  must  express  conclusions  with  all 
reserve.  The  patient  was  a  healthy  man  who  died 
two  and  a  half  hours  after  a  fall  from  a  ladder  which 
caused  a  fractured  pelvis,  fractured  humerus,  and 
retroperitoneal  hematoma.  The  brain-stem  and 
cerebellum  were  removed,  hardened  in  formalin, 
sectioned  with  the  freezing  microtome,  and  stained  by 
Nissl's  method.  The  examination  of  a  number  of 
sections  showed  the  following  changes.  Purkinje  cells 
of  cerebellum  :  all  full  of  Nissl  granules ;  no  abnormal 
cells  found  in  some  hundreds  examined.  Cells  of 
dentate  nucleus  of  cerebellum  :  practically  all  normal. 
Cells  of  various  motor  nuclei  in  medulla  :  all  normal. 
Cells  of  inferior  olive  :  the  majority  normal ;  a  few 


48  SURGICAL    SHOCK 

showed  reduction  of  Nissl  granules.  Cells  of  Deiiers' 
nucleus  (lateral  vestibular)  :  some  normal  cells ; 
majority  showed  considerable  reduction  of  the 
granules,  and  many  cells  had  practically  none  left. 
Cells  of  gracile  and  cuneate  nuclei :  very  remarkable 
absence  of  Nissl  granules  :  scarcely  a  granule  to  be 
found  in  the  whole  nucleus.  We  know  that  reduc- 
tion of  the  Nissl  granules  is  usually  an  evidence  of 
exhaustion  of  nerve-cells,  but  it  must  distinctly  be 
understood  that  we  have  no  evidence  that  if  a  nerve 
cell  is  paralyzed  it  must  necessarily  show  histological 
changes,  and  absence  of  chromatolysis  would  not 
therefore  prove  that  certain  nuclei  were  able  to 
function  properly. 

THE     DIAGNOSIS,    TREATMENT,     AND     PRE- 
VENTION    OF     SHOCK. 

It  must  regretfully  be  admitted  that  such  a  con- 
ception of  shock  makes  diagnosis  and  treatment 
much  more  difficult.  And  first,  diagnosis  is  difficult 
because  we  may  no  longer  place  implicit  reliance 
upon  the  blood-pressure.  No  doubt  a  fall  of  pressure 
is  our  best  sign  of  shock,  but  it  ceases  to  be  infallible. 
For  instance,  crushing  the  testis  may  induce  a  reflex 
depression  through  the  vasomotor  centre,  which  is 
perfectly  recoverable  without  any  other  symptom  of 
shock.  Again,  and  surely  we  have  all  learned  only 
too  well  the  truth  of  this,  a  patient  may  be  far  worse 
than  the  pulse  and  pressure  would  lead  one  to  think. 
A  diagnosis  of  shock  nowadays  must  take  into 
account  the  whole  clinical  picture  described  by 
Sir  Watson  Cheyne,  as  well  as  the  readings  of  the 
sphygmomanometer , 


SURGICAL    SHOCK  49 

In  the  treatment  of  shock,  the  failure  of  the  simpler 
theories  leaves  us  sadly  bereft  of  our  weapons  for 
meeting  it.  It  was  so  easy  to  give  pituitary  extract 
for  paralyzed  vasomotors,  carbon  dioxide  for 
acapnia,  intravenous  or  subcutaneous  saline  for 
oligemia,  and  adrenalin  injections  for  exhaustion  of 
the  suprarenals,  and  so  hard  to  understand  why 
they  might  one  and  all  fail.  But  what  can  one  do 
for  paralysis  of  the  nerve-cells  of  all  the  vital  centres  ? 
Evidently  it  is  not  enough  merely  to  raise  the  blood- 
pressure,  although  that  may  help  a  little  by  driving 
more  blood  to  the  brain,  and  so  give  the  damaged 
nerve-cells  the  most  favourable  conditions  for 
recovery.  Saline  transfusion  or  infusion  has  its 
value  in  maintaining  the  output  of  the  heart.  Re- 
cently the  use  of  sodium  bicarbonate  instead  of 
chloride  has  been  advocated  by  several  American 
writers  on  experimental  grounds,  though  they  find 
it  hard  to  give  a  satisfactory  explanation  of  its 
action. 

It  is  doubtful  if  pituitary  extract  or  adrenalin  do 
any  good,  and  Crile's  teaching  as  to  the  futility  of 
strychnine  and  alcohol  is  probably  correct.  Happily 
it  is  possible,  to  some  extent,  to  exert  pressure  on 
the  dilated  veins  and  so  replace  the  deficient  muscular 
tone  by  means  of  elastic  bandages  for  the  limbs  and 
abdomen,  taking  care  not  to  impede  the  action  of 
the  diaphragm.  Intraperitoneal  saline  fluid  in  large 
quantity  would  help  in  the  same  way.  In  cases  of 
shock  from  burns,  the  indications  for  introducing 
plenty  of  saline  are  clear. 

It  is  to  the  prevention  of  shock  that  we  must  look 

4 


50  SURGICAL    SHOCK 

with  some  degree  of  confidence  for  the  future.  And 
here  lies  the  abiding  value  of  Professor  Crile's  work. 
His  conception  is  that  general  anaesthetics,  whilst 
they  protect  the  cerebral  cortex  from  painful  impulses, 
do  not  afford  much  protection  to  the  lower  level 
centres  in  the  brain-stem.  Inasmuch  as  the  cutting, 
crushing,  dragging,  burning,  or  other  injuries  inflicted 
on  the  limbs  or  viscera  cannot  be  spoken  of  as  painful 
when  owing  to  the  ether  or  chloroform  no  pain  is 
felt,  these  are  described  as  "  nociceptive  "  impulses 
(Sherrington).  Crile's  method  is  to  prevent  the 
origin  or  block  the  path  of  the  nociceptive  impulses 
by  means  of  local  anaesthetics,  principally  novocain 
for  the  skin,  nerve-trunks,  and  subcutaneous  tissues, 
and  quinine-urea-hydrochloride  for  the  peritoneum. 
Although  the  patient  is  under  a  general  anaesthetic, 
the  line  of  skin  incision  is  injected  with  novocain. 
In  an  amputation,  the  main  nerves  are  blocked  with 
the  same  drug.  All  suture  lines  and  cut  edges  of 
the  peritoneum  are  mopped  with  the  quinine-urea- 
HC1  solution  (0-5  per  cent  of  each)  before  and 
afterwards.  Intraspinal  anaesthesia  is  of  course  an 
extension  of  the  method. 

Further,  all  manipulations  must  be  conducted 
with  the  most  extreme  gentleness.  Crile  protests 
very  strongly  against  what  he  calls  "  carnivorous  " 
surgery.  And,  thirdly,  he  finds  that  nitrous-oxide- 
oxygen  produces  much  less  chromatolysis  of  nerve- 
cells  than  ether  or  chloroform,  and  therefore  uses 
it  for  nearly  all  operations. 

The  results,  though  not  yet  perfect,  are  most 
promising.     Shock    is    greatly    diminished,    painful 


SURGICAL    SHOCK  51 

post-operative  flatulence,  due  to  intestinal  paralysis 
reflexly  induced  by  the  injury  to  the  peritoneum,  is 
more  or  less  completely  abolished,  and  the  death-rate 
is  reduced.  The  writer  can  testify  by  personal 
experience  to  the  truth  of  these  claims  ;  the  comfort 
after  a  big  abdominal  operation  is  sometimes  most 
remarkable. 

Nevertheless,  something  remains  to  be  desired. 
The  local  anaesthetics  are  not  yet  perfect  in  their 
action.  Case  i,  recorded  above,  died  of  shock  in 
spite  of  very  thorough  use  of  these  methods  (called 
by  Crile  "  anoci-association  ").  Quinine-urea-hydro- 
chloride,  which  is  used  for  the  peritoneum  instead 
of  novocain  because  the  anaesthesia  is  more  long- 
lasting,  has  the  great  drawback  of  being  destructive 
to  the  tissues,  and  may  cause  trouble  with  the  wound 
or  even  impair  the  security  of  an  intestinal  anasto- 
mosis. However,  it  ought  not  to  be  an  insoluble 
problem  for  the  chemist  to  produce  a  more  powerful, 
long-lasting,  non-destructive  local  anaesthetic,  and 
when  this  is  in  our  hands  the  prevention  of  surgical 
shock  will  be  as  feasible  as  the  triumph  over  those 
three  conquered  foes,  haemorrhage,  pain,  and  sepsis. 

INTRAVENOUS     SALINE     TRANSFUSION. 

During  the  past  few  years,  the  scope  for  this 
proceeding  has  been  enlarged  considerably  by  the 
introduction  of  the  intravenous  methods  of  giving  sal- 
varsan  for  syphilis,  or  ether  as  a  general  anaesthetic  ; 
and  Rogers  reports  great  benefit  from  the  injection  of 
hypertonic  saline  solutions  for  cholera.  The  success 
which  has   attended   its   use   in  the    treatment   of 


52  SURGICAL    SHOCK 

shock,  and  especially  of  collapse  after  haemorrhage, 
has  caused  it  to  be  used  more  and  more  extensively 
for  these  conditions.  At  the  same  time,  some  very 
serious  drawbacks,  in  a  degree  avoidable,  have  come 
to  light,  and  with  these  we  must  now  deal. 

We  need  barely  mention  the  difficulty  of  finding 
and  introducing  the  cannula  into  the  vein,  the  danger 
of  injecting  air-bubbles,  and  the  necessity,  when  the 
solution  is  made  up  in  a  private  house,  of  using  cook- 
ing salt,  and  not  a  table  salt  diluted  with  farinaceous 
or  other  material.  More  care  is  necessary  than  is 
usually  taken  to  see  that  the  temperature  at  which 
the  fluid  enters  the  vein  is  correct ;  that  of  the  saline 
in  the  funnel  may  be  many  degrees  higher,  especially 
at  first.  It  is  easy  to  let  the  solution  flow  over  the 
bulb  of  a  thermometer  before  introducing  the  cannula. 
Then,  again,  the  proper  strength  of  sodium  chloride 
(o'9  per  cent ;  a  teaspoonful  and  a  half  to  the  pint) 
must  be  employed.  It  is  far  more  physiological  to 
use  Ringer's  fluid,  containing  calcium  and  potassium 
salts  as  well,  with  a  little  dextrose  added  to  act  as  a 
food-stuff.  Compressed  tablets  of  the  correct  com- 
position are  upon  the  market.  This  fluid  approxi- 
mates more  nearly  to  that  of  plasma,  and  is  capable  of 
maintaining  the  life  and  activity  of  the  tissues  much 
longer  than  simple  saline  will. 

There  are  two  dangers  which  may  follow  the  trans- 
fusion. The  first  depends  upon  the  water,  and  the 
second  upon  the  salt.  Wechselmann  in  Germany, 
and  Hort  and  Penfold  in  England,  have  pointed  out 
that  water  supposed  to  be  sterile  usually  produces 
shivering  and  fever  in  animals,  and  frequently  in 


SURGICAL    SHOCK  53 

man,  after  intravenous  transfusion  or  subcutaneous 
injection.  In  Wechselmann's  cases  this  was  usually- 
due  to  actual  contamination  with  bacteria  during  the 
days  or  weeks  that  the  water  was  left  standing  after 
distillation.  The  English  observers  found  that 
although  water  just  distilled  and  collected  in  a  glass 
retort  produced  no  fever,  yet  within  a  few  days  after 
standing  in  sealed  sterile  vessels  it  acquired  the 
property  of  giving  rise  to  fever,  and  that  in  spite 
of  boiling  or  filtration  through  a  Berkefeldt  filter 
immediately  before  use.  In  some  cases  the  tempera- 
ture was  high,  but  not  fatal  unless  quite  unsuitable 
injections  were  given. 

Another  danger  depends  on  the  salt  used.  The 
total  quantity  injected  may  be  very  large — ten  grams 
or  more.  A  condition  of  hydremic  plethora  is  likely 
to  be  induced,  that  is,  a  dilution  and  increase  in  the 
total  volume  of  the  blood.  As  Lazarus  Barlow  has 
shown,  the  specific  gravity  at  once  falls  (e.g.,  from 
1*064  to  I,054)-  The  kidneys  and  lymph  channels 
promptly  excrete  the  excess  of  fluid,  and  in  many 
cases  overshoot  the  mark,  so  that  eventually  the 
specific  gravity  may  be  1*067,  signifying  of  course 
that  the  blood  is  less  in  bulk  and  more  concentrated 
than  it  was  before.  This  does  not  occur  if  the 
supply  of  fluid  is  kept  up  by  further  injections,  or 
saline  given  by  the  bowel. 

If  the  kidneys  are  not  capable  of  excreting  the 
water  and  salt  quickly  enough,  some  degree  of  dropsy 
may  occur,  and  as  the  Griinbaums  have  pointed  out, 
this  may  take  the  form  of  fatal  oedema  of  the  lungs, 
which  has  frequently  been  described  as  following  saline 


54  SURGICAL    SHOCK 

transfusion,  especially  in  patients  with  nephritis.  The 
Griinbaums  consider  that  the  use  of  ether  as  an 
anaesthetic  helps  to  determine  the  occurrence  of  such 
pulmonary  oedema.  If  the  salt  solution  injected  was 
too  concentrated,  a  greater  degree  of  hydrsemic  ple- 
thora is  induced,  and  the  risks  of  pulmonary  oedema 
are  increased  ;  naturally  it  is  more  likely  to  occur 
after  a  large  injection  than  a  small  one. 

These  unfavourable  possibilities  are  not  mentioned 
to  proscribe  the  use  of  saline  transfusion,  but  to  call 
attention  to  the  best  methods  of  avoiding  complica- 
tions. Of  the  last  eight  cases  in  which  it  has  been 
used  at  the  Bristol  Royal  Infirmary,  only  one  (a  case 
of  mesenteric  thrombosis)  died,  although  the  treat- 
ment is  reserved  for  the  most  desperate  conditions, 
especially  haemorrhage,  and  most  of  the  patients  were 
pulseless.  In  these  cases  it  does  not  appear  to  have 
produced  either  fever  or  lung  complications,  although 
a  solution  which  had  been  standing  was  used. 
Several  of  the  patients,  however,  had  fever  before  the 
injection  began,  and  this  continued.  Not  more  than 
one  or  two  pints  were  used,  and  this  was  followed 
up  by  saline  per  rectum  in  most  instances. 

To  obtain  the  best  results  and  the  fewest  fatalities 
not  more  than  thirty  or  forty  ounces  of  freshly 
distilled  water,  collected  in  a  sterile  glass  vessel, 
should  be  injected.  In  this  a  powder  having  the 
composition  of  Ringer's  fluid,  with  dextrose,  should 
be  dissolved.  The  powder  must  be  sterilized  or  the 
solution  boiled.  The  transfusion  must  be  made 
slowly,  and  at  a  suitable  temperature  (ioo°  F.), 
and  it  should  be  followed  by  saline  injections  per 


SURGICAL    SHOCK  65 

rectum  to  avoid  the  reversal  of  the  effect.  If  Bright' s 
disease  is  known  to  be  present,  the  treatment  should 
be  used  only  when  the  need  is  desperate. 

Unfortunately,  saline  transfusion  is  usually  wanted 
at  a  moment's  notice,  and  a  freshly  distilled  water 
may  not  be  obtainable.  It  is  fortunate  therefore 
that  the  effects  are  not  likely  to  be  very  serious  even 
if  a  stale  but  sterile  sample  has  to  be  used. 

What  has  been  said  with  regard  to  intravenous 
transfusion  applies  also  to  subcutaneous  injection. 

It  is  becoming  increasingly  common  to  replace 
some  of  the  sodium  chloride  in  saline  solutions  given 
by  the  bowel  by  glucose,  which  acts  as  a  food.  Two 
drachms  of  glucose  with  one  drachm  of  salt  may  be 
dissolved  in  a  pint  of  water.  Stronger  solutions  of 
glucose  are  apt  to  be  irritating  to  the  bowel. 

REFERENCES. 

Rendle    Short. — "  Hunterian   Lecture/'    Lancet,    1914,     i, 

p.  371.     (Includes  full  bibliography.) 
Hort    and    Penfold. — Brit.  Med.  Jour.,  1911,  ii,  p.   1589. 
Grunbaum,  A.  S.  and  H. — Brit.  Med.  Jour.,  191 1,  ii,  p.  1281. 


56 


CHAPTER    IV. 
THE     GROWTH     OF     BONE. 

Recent  change  in  our  conception  of  the  growth  of  bone — -Osteo- 
blasts— Increase  in  the  length  of  bone — Increase  in  the  girth  of 
bone — Function  of  the  periosteum — The  regenerative  powers  of 
bone — Transplantation  of  bone — Application  of  modern  researches 
to  surgical  practice — Relation  of  the  ductless  glands  to  the  growth 
of  bone. 

TWO  closely  allied  problems,  how  bones  increase  in 
length  and  girth  in  the  child,  and  how  regenera- 
tion of  new  bone  takes  place  after  loss  or  injury,  are 
of  great  interest  and  practical  importance  in  surgery. 
Every  case  of  separation  of  an  epiphysis  by  accident, 
and  every  operation  on  the  growing  end  of  a  bone 
in  children,  involves  a  consideration  of  the  first 
problem  ;  every  case  of  fracture,  necrosis,  periostitis, 
or  osteomyelitis  depends  for  its  proper  understand- 
ing and  rational  treatment  upon  the  second.  A  very 
important  research  has  recently  been  published  which 
necessitates  a  radical  change  in  some  of  our  con- 
ceptions of  this  subject. 

We  may  summarize  the  traditional  teaching  thus. 
Bone  is  laid  down  by  certain  cells  called  osteoblasts. 
In  young  animals,  these  are  the  direct  descendants 
of  cartilage  cells.  When  the  cartilage  becomes 
vascular,  the  cells  undergo  proliferation  for  a  time  ; 
when  they  assume  their  individual  maturity  they 
cease  to  divide,  and  lay  down  calcareous  salts  all 


THE    GROWTH    OP    BONE  57 

around  themselves  just  as  a  coral  polyp  does ;  they 
are  included  in  the  midst  of  the  bone  thus  formed  as 
bone  corpuscles. 

Increase  in  the  length  of  the  bone  takes  place  by 
the  new  additions  at  each  end,  where  the  layer  of 
cartilage  between  the  shaft  and  the  epiphysis  is  con- 
stantly being  transformed  into  bone  ;  but  inasmuch 
as  its  cells  keep  on  dividing,  the  cartilage  is  not  used 
up  in  the  process  until  the  age  of  eighteen  to  twenty- 
five  is  reached.  It  is  usual  for  one  epiphysis  to  unite 
later  than  the  other,  and  in  that  case  the  increase  of 
length  is  greater  at  this  end  than  at  the  opposite,  and 
the  nutrient  artery  to  the  shaft  will  be  directed  away 
from  the  persistent  epiphysis  because  the  bone  is,  as 
it  were,  pushed  down  inside  the  periosteum. 

So  far,  the  results  of  recent  investigation  entirely 
support  and  amplify  the  older  opinion.  A  classical 
experiment  of  John  Hunter's  may  be  quoted.  He 
inserted  two  leaden  shot  into  the  tibia  of  a  young 
pig,  exactly  two  inches  apart.  When  the  animal  had 
grown  up,  he  found  that  although  the  bone  was  of 
course  much  longer,  the  shot  were  still  exactly  two 
inches  apart.  Evidently,  then,  the  increase  of  length 
must  have  been  at  the  ends,  not  by  interstitial 
increase  of  the  shaft. 

More  recently,  Macewen  has  removed  almost  the 
whole  shaft  of  the  right  radius  in  a  young  dog  by 
the  subperiosteal  method,  leaving  the  two  ends. 
After  six  weeks,  there  was  strong  and  vigorous  growth 
from  each  epiphysis,  and,  aided  by  a  bending  of  the 
ulna,  the  two  ends  had  come  together,  although  no 
periosteal  growth  of  bone  had  taken  place.    One  of 


58  THE    GROWTH    OF    BONE 

the  epiphyses  was  damaged ;  from  this  end  the  new 
bony  development  was  slenderer  than  from  the  un- 
injured end. 

In  another  experiment,  two  and  a  half  inches  of 
bone  with  its  periosteum  were  removed  from  the 
radius  of  a  young  dog,  and  metal  caps  fitted  over 
the  sawn  extremities  of  the  shaft  remaining  in  situ. 
Seven  weeks  later,  the  gap  was  found  completely 
bridged  by  bone,  and  the  two  metal  caps  had  come 
together.  Owing  to  bending  of  the  ulna,  they  did 
not  absolutely  meet,  but  passed  one  another  laterally. 

In  yet  another  case,  the  plate  of  cartilage  between 
the  shaft  and  epiphysis  was  removed  from  the  radius 
of  a  young  dog.  The  bone  failed  to  grow  at  that  end, 
and  a  lateral  expansion  of  the  epiphysis  became 
attached  to  the  ulna  and  stunted  its  growth  also. 
This  experiment  is  of  course  paralleled  in  man, 
when  a  separation  of  an  epiphysis  takes  place,  or 
when  the  growing  end  is  removed  in  the  excision  of 
a  joint. 

Increase  in  the  girth  of  bone  has  been  attributed  to 
the  periosteum.  Between  it  and  the  bone,  osteoblasts 
are  to  be  found  in  young  animals,  and  these  lay  down 
ring  after  ring  of  concentric  lamellae.  If  the  develop- 
ing animal  is  fed  with  pigment,  such  as  madder,  for  a 
short  period,  there  may  be  found  months  later  a 
buried  pigmented  ring  of  bone  which  was  laid  down 
at  that  time.  Another  classical  experiment  we  owe  to 
Duhamel  (1739),  who  buried  a  silver  ring  under  the 
periosteum  of  a  young  animal,  and  found  some  time 
after  that  the  ring  had  become  covered  by  subsequent 
bone  formation. 


THE    GROWTH    OF    BONE  59 

It  was  the  natural  corollary  from  this  belief,  that 
when  bone  has  been  destroyed  by  inflammation  or 
removed  by  operation,  we  must  look  to  the  periosteum 
to  regenerate  new  bone  ;  and  as  a  matter  of  fact  it  is 
well  known  that  if  the  periosteum  is  stripped  up  from 
the  shaft  by  a  purulent  collection  beneath  it,  it  does 
in  most  cases  lay  down  a  sheath  of  bone  outside  the 
space  in  which  the  pus  lay.  Again,  after  fractures 
we  look  to  the  periosteum  to  produce  ensheathing 
callus  to  bind  the  broken  ends  together  again.  Some 
regenerating  power,  however,  must  be  allowed  to 
osteoblasts  derived  from  the  bone  itself,  to  explain 
the  formation  of  callus  between  the  actual  fractured 
ends  and  in  the  medullary  cavity. 

Well  entrenched  as  this  view  has  been,  it  has 
recently  been  subjected  to  most  damaging  criticism 
by  Sir  William  Macewen,  who  goes  so  far  as  to  state 
that  the  function  of  the  periosteum  is  not  to  produce 
bone  but  to  limit  the  production  of  bone,  and  that 
osseous  regeneration  takes  place  from  the  osteoblasts 
of  the  bone  itself,  not  from  the  periosteum.  He 
supports  his  thesis  by  some  most  interesting  experi- 
ments on  animals,  and  observations  on  man. 

It  has  always  been  admitted  that  some  power  of 
laying  down  bone  must  be  allowed  to  osteoblasts 
quite  apart  from  the  epiphyseal  cartilages  or  the 
periosteum,  because  of  course  it  is  their  province  to 
fill  in  the  Haversian  canals  with  concentric  rings  of 
new  bone,  and  also  to  cement  the  ends  of  a  fracture 
as  intermediary  and  intramedullary  callus.  The  hard- 
ness and  density  of  bone  rather  blind  our  eyes  to  the 
fact  that,  like  every  other  living  tissue,  the  processes 


60  THE    GROWTH    OF    BONE 

of  building  up  and  breaking  down,  absorption  and 
new  formation,  are  continually  going  on  in  its  cells 
and  molecules.  When  it  is  irritated,  as  for  instance 
when  a  pin  is  driven  into  compact  bone,  absorption 
takes  place,  and  the  pin  loosens  in  the  course  of  a  day 
or  two  ;  when  it  is  withdrawn,  osteoblasts  wander 
into  the  track  and  rill  it  with  new  bone.  Even  so  soft 
an  organ  as  the  tongue  helps  to  maintain  the  shape  of 
the  jaw,  and  after  a  successful  operation  for  cancer, 
the  lower  teeth  come  in  time  to  slope  towards  the 
buccal  cavity.  The  interstitial  changes  in  bone  are 
affected  by  various  toxins  and  internal  secretions  : 
during  rickets  the  osseous  tissue  is  at  first  softened, 
finally  more  compact ;  the  pituitary  secretion  causes 
it  to  undergo  hypertrophy. 

So  much  is  known  and  admitted.  The  evidence 
which  enables  Macewen  to  go  further  and  to  deny 
any  share  to  the  periosteum  as  such,  is  as  follows: — ■ 

In  a  dog,  a  strip  of  periosteum  a  quarter  of  an 
inch  broad  and  two  inches  long  was  peeled  up  from 
the  radius,  leaving  the  attachment  to  the  epiphysis 
intact.     It  was  buried  between  muscles. 

Eight  weeks  later,  there  was  no  trace  of  bone 
formation  in  the  fibrous  intermuscular  band  which 
represented  the  periosteum.  On  the  other  hand, 
there  was  a  bony  ridge  outgrown  from  the  area 
whence  it  had  been  stripped  up.  So  far  then  from 
forming  bone,  the  periosteum  must  have  been  pre- 
venting the  outgrowth  of  bone. 

In  other  experiments,  a  strip  of  periosteum  was 
excised  and  immediately  implanted  in  the  neck  of  the 
same  animal  around  the  jugular  vein.     Usually  it 


THE    GROWTH    OF    BONE  61 

absorbed  completely ;  once  a  tiny  osseous  nodule 
was  found,  derived  probably  from  an  attached  chip 
of  bone.  Macewen  points  out  the  great  practical 
importance  of  this  in  such  an  operation  as  sub- 
periosteal excision  of  the  elbow.  If  care  is  not  taken 
to  inspect  the  periosteum,  adherent  bony  flakes  may 
be  left  which  will  grow,  and  lock  the  joint.  If  they 
are  all  removed,  an  excellent  free  joint  results.  This 
represents  the  experience  of  over  two  hundred 
cases.  On  the  other  hand,  care  must  be  taken 
not  to  encroach  on  the  diaphysis  of  the  humerus  by 
removing  too  much,  or  it  may  sprout  new  bone. 

In  other  experiments,  Macewen  removed  portions 
or  the  whole  length  of  a  bone  subperiosteally.  No 
regeneration  took  place  to  fill  the  gap,  except  in  a 
few  cases  where  the  animal  was  young,  and  the  grow- 
ing epiphyseal  ends  pushed  the  extremities  together 
to  diminish  or  obliterate  the  gap.  No  new  periosteal 
bone  was  formed. 

He  then  repeated  Duhamel's  silver-ring  observa- 
tion, and  found  that  the  burying  beneath  new  osseous 
tissue  occurred  just  as  well  if  the  bone  in  that  neigh- 
bourhood, or  indeed  in  its  whole  length,  was  first 
deprived  of  periosteum.  The  new  bone  could  be 
seen  overflowing  the  ring  from  the  edges.  In  this 
case  it  is  perfectly  evident  that  the  osteoblasts 
providing  for  growth  must  have  come  from  the  shaft, 
not  from  the  periosteum. 

A  number  of  important  observations  are  recorded,, 
demonstrating  the  regenerative  powers  of  bone  itself, 
apart  from  periosteum,  and  more  particularly  in 
young  animals.     These  may  be  briefly  summarized. 


62  THE    GROWTH    OF    BONE 

Although  grafts  of  periosteum  into  the  neck  will  not 
grow  osseous  tissue,  thin  shavings  of  bone  itself, 
similarly  transplanted,  will  double  in  length  and 
thickness  in  most  cases.  In  a  number  of  experiments, 
pieces  of  bone  an  inch  or  more  in  length,  or  even 
comprising  the  whole  shaft  of  a  long  bone,  were 
successfully  transplanted  from  one  dog  to  another. 
In  a  classical  case,  Macewen  built  up  a  new  humerus 
for  a  lad  who  had  lost  the  shaft  by  acute  necrosis, 
and  although  the  wedges  of  bone,  derived  from 
excisions  for  deformed  legs,  were  not  covered  with 
periosteum,  they  grew  and  consolidated,  and  now, 
more  than  thirty  years  after,  aided  by  the  great 
growth  of  the  upper  epiphysis  which  has  contributed 
the  bulk  of  the  humerus,  the  arm  is  strong  and 
useful.  In  other  cases,  fragments  of  bone  have  been 
replaced  to  fill  gaps  in  the  skull,  with  excellent 
results. 

Many  surgeons  besides  Macewen  have  achieved 
success  with  bone  transplantation.  For  instance,  a 
piece  of  the  fibula  has  been  inserted  to  supply  the 
defect  in  the  humerus  left  by  the  removal  of  an  intra- 
osseous cyst,  and  consolidation  took  place.  The 
lower  jaw  and  the  tibia  have  several  times  been 
replaced  in  similar  fashion  by  bone  grafts  from  the 
same  patient. 

Macewen  has  secured  osseous  growth  by  trans- 
plantation of  bone  chips  into  the  omentum,  and  also, 
after  burying  glass  tubes  in  the  middle  of  a  long 
bone,  he  has  found  the  lumen  of  the  tube  invaded  by 
osteoblasts,  and  osseous  islands  laid  down.  In  one 
interesting  case,  a  traumatic  aneurysm  formed  from 


THE    GROWTH    OF    BONE  63 

the  brachial  artery  of  a  young  patient  in  consequence 
of  the  penetration  of  the  vessel  by  a  spicule  of  the 
humerus,  which  was  fractured.  Osteoblasts  washed 
out  of  the  humerus  were  thus  distributed  throughout 
the  clot  lining  the  aneurysm,  and  it  developed  a 
regular  bony  wall.  This  would  probably  occur  more 
frequently  when  the  aorta  erodes  the  vertebrae,  but 
for  the  fact  that  in  that  case  the  patient's  osteoblasts 
are  usually  senile. 

In  some  experiments,  after  removing  a  length  of 
the  radius  with  its  periosteum,  the  gap  was  filled 
with  bone  chips.  Consolidation  took  place,  but  a 
large  tumour-like  mass  of  callus  formed,  infiltrating 
the  surrounding  muscles.  The  osteoblasts  from  each 
chip  had  wandered  out  and  proliferated,  and  when 
they  became  mature  had  surrounded  themselves 
with  calcareous  deposit,  which  bound  together  not 
only  the  detached  fragments  and  the  broken  ends, 
but  also  the  muscles  and  tendons  in  the  neighbour- 
hood. 

The  experimental  and  clinical  work  of  Hey  Groves 
on  fractures  strongly  supports  the  view  that  callus  is 
derived  from  bone  and  not  from  periosteum. 

The  factors  which  induce  bone-corpuscles  to 
become  active  and  proliferate  are  not  perfectly 
understood.  Macewen  lays  stress  on  relief  from 
pressure,  and  no  doubt  this  has  great  importance. 
Dissemination  of  osteoblasts  by  increased  vascularity 
of  the  part  is  another  factor.  The  periosteum,  when 
intact,  limits  the  osteoblasts  to  their  own  proper 
sphere,  and  prevents  their  encroaching  on  the 
muscles  and  fascial  planes. 


64  THE    GROWTH    OF    BONE 

According  to  some  German  and  French  observa- 
tions, blood-clot  has  an  influence  not  only  in  pro- 
viding a  suitable  medium  in  which  bone  may  be 
formed,  but  further,  in  exerting  a  direct  chemical 
stimulus  upon  the  osteoblasts. 

We  may  now  apply  these  researches  to  surgical 
practice,  considering  first  the  consequences  and 
repair  of  fractures.  In  subperiosteal  fractures,  rapid 
and  firm  union  takes  place  without  any  ensheathing 
callus,  and  the  bone  feels  quite  normal  after  a  few 
months.  When  the  periosteum  is  extensively  torn, 
osteoblasts  wander  out  beyond  its  limits,  and  en- 
sheathing callus  may  be  formed  in  quantity.  Much 
will  depend  on  the  amount  of  movement  to  which 
the  part  is  subjected.  Vigorous  movement,  or,  in 
those  cases  where  the  periosteum  is  stripped  away, 
deep  massage  applied  too  early  just  over  the  site  of 
the  fracture,  will  disseminate  the  osteoblasts  far  and 
wide.  Not  only  may  the  callus  be  excessive,  and, 
perchance,  lock  the  nearest  joint,  but  muscles,  nerves, 
or  tendons  may  become  ensheathed  by  new  bone, 
and  their  functions  be  impaired. 

Here  belong  those  interesting  and  by  no  means 
infrequent  cases  in  which,  after  a  fracture,  especially 
near  the  elbow  joint,  an  osseous  mass  develops  in  the 
muscles,  as  for  instance  in  the  brachialis  anticus. 
This  is  called  traumatic  myositis  ossificans.  The  mass 
can  be  moved  apart  from  the  bone,  and  casts  a 
shadow  with  the  #-rays.  What  has  happened  is  that 
massage  or  movements  have  scattered  the  osteoblasts 
far  and  wide,  and  they  have,  after  a  few  weeks, 
performed'their  usual  function,  and  regenerated  bone 


THE    GROWTH    OF    BONE  65 

in  their  new  surroundings.  It  is  significant  that 
these  cases  have  become  common  only  since  the 
modern  treatment  by  massage  and  movements 
has  been  introduced,  excellent  as  it  is  when  suitably 
applied.  If  the  periosteum  had  remained  intact,  this 
could  never  have  occurred.  The  treatment,  if  such 
a  lump  forms,  is  not  excision,  which  usually  leads 
to  recurrence,  but  strict  limitation  of  movement  by 
means  of  a  splint. 

The  reason  why  so  much  more  callus  forms  in 
animals  than  in  man  is  because  so  much  more 
movement  of  the  broken  ends  takes  place.  In  these 
circumstances  there  is  often  a  stage  in  which  cartilage 
is  to  be  found  in  the  callus,  on  its  way  to  form  bone. 

It  is  evident,  therefore,  that  care  should  be  exer- 
cised, after  a  fracture  in  which  it  is  probable  that  the 
periosteum  is  torn,  to  avoid  deep  massage  and  move- 
ments close  to  the  site  of  the  fracture  during  the  first 
fortnight,  although  they  may  well  be  applied  to  the 
neighbouring  joints.  When  the  fracture  is  very  near 
a  joint  it  is  far  better  to  trust  to  a  single  efficient 
movement  once  a  week  (to  avoid  adhesions)  than  to 
allow  repeated  small  movements  in  the  early  stages. 

It  is  well  known  that  exostoses  or  spurs  of  bone 
usually  form  in  the  attachment  of  muscles  or  tendons. 
The  probable  explanation  is  that  by  the  continual 
drag  and,  it  may  be,  slight  wrenches,  some  osteo- 
blasts are  detached  from  the  bone  and  invade  the 
tendon. 

Universal  myositis  ossificans,  such  as  occurs  in  a 
so-called  "  brittle  man,"  may  be  due  to  some  such 
cause  as  this,  or  perhaps  to  embolism  of  osteoblasts. 

5 


66  THE     GROWTH     OP    BONE 

The  strongest  evidence  for  the  older  view,  that 
bone  is  laid  down  by  the  periosteum,  is  provided  by- 
cases  of  acute  periostitis,  where  pus  forming  inside 
the  bone  finds  its  way  out  between  the  shaft  and  the 
periosteum,  so  that  the  latter  is  extensively  stripped 
up.  In  many  cases,  new  bone  begins  to  form  under 
the  detached  periosteum,  outside  the  pus,  and  the 
shaft  usually  necroses. 

Macewen  explains  this  occurrence  by  declaring 
that  if  the  inflammatory  mischief  is  not  very  acute, 
vasodilatation  takes  place  within  the  bone,  and  the 
osteoblasts  are  carried  out  by  the  Haversian  canals 
to  the  loose  areolar  space  under  the  periosteum,  to 
which  fibrous  membrane  some  of  them  adhere. 
When  this  is  stripped  up  later,  these  osteoblasts  lay 
down  new  bone,  but  those  remaining  on  the  shaft  are 
deprived  of  their  blood-supply  and  therefore  die.  If 
the  inflammatory  mischief  in  the  centre  of  the  bone 
is  very  acute,  the  whole  shaft  may  die,  especially  if 
thrombosis  occurs,  and  therefore  no  osteoblasts 
escape,  so  that  no  new  bone  at  all  can  be  laid  down 
under  the  periosteum.  This  is  by  no  means  a  rare 
occurrence. 

In  local  periostitis,  again,  which  should  rather  be 
described  as  an  osteitis,  the  bone-forming  cells  are 
brought  by  the  blood-stream  to  the  loose  areolar 
tissue  underneath  the  periosteum,  and  finding  there 
a  line  of  least  resistance,  are  able  to  lay  down 
young  bone,  and  so  produce  a  localized  swelling, 
marked  out  in  a  skiagram  by  a  faint  line  of  shadow 
close  to,  and  parallel  with,  the  shaft. 

During  operations  for  the  removal  of  bone,  great 


THE    GROWTH    OF    BONE  67 

efforts  are  often  made  to  preserve  the  periosteum, 
and  sometimes,  as  for  instance  in  excising  the  lower 
jaw,  the  membrane  is  preserved  even  at  the  risk  of 
leaving  septic  material  behind,  in  the  vain  hope  that 
it  will  form  new  bone.  The  only  possibility  of  its 
doing  so  is  if  osteoblasts  have  been  driven  out  by 
inflammation  and  have  become  adherent  to  it.  It  is 
useless  to  expect  healthy  periosteum  to  regenerate 
bone,  such  as  a  piece  of  rib  removed  for  empyema, 
though  it  may  form  a  guide  for  the  gap  to  be  filled 
by  growth  from  the  epiphyseal  end. 

Bone  transplantation  has  now  reached  a  thoroughly 
established  position,  and  scores  of  successes  have 
been  reported.  Parts  of  the  tibia,  humerus,  skull, 
and  lower  jaw  have  repeatedly  been  replaced  by 
slips  from  the  fibula,  rib,  or  other  situations.  Some- 
times it  is  possible  to  maintain  the  blood-supply  by 
preserving  the  periosteum  and  soft  tissues  over  the 
graft  with  a  pedicle,  as  when  the  fibula  is  put  into  a 
gap  in  the  tibia.  In  other  cases  the  strip  of  bone  or 
the  bone  chips  have  to  be  detached  entirely,  or  even 
transplanted  from  patient  to  patient,  but  they  will 
frequently  survive  in  part  or  in  whole,  acquire  a  new 
blood-supply,  and  unite  up  with  the  divided  ends. 
Very  small  chips  or  bone  dust  are  not  successful, 
apparently  because  the  osteoblasts  are  damaged ; 
on  the  other  hand,  thick  pieces  of  bone  will  die.  If 
in  any  way  possible,  the  graft  should  be  taken  from 
a  young  growing  bone,  especially  that  near  the 
epiphyseal  cartilage.  Perhaps  pieces  of  epiphyseal 
cartilage  itself  would  be  best  of  all,  because  it  is 
content  with  a  very  small  blood-supply. 


68  THE    GROWTH    OF    BONE 

There  is  some  relationship,  not  well  understood, 
between  the  internal  secretions  of  the  ductless  glands 
and  the  growth  of  bone.  Over-secretion  of  the 
pituitary  gland,  as  we  shall  see,  results  in  overgrowth 
of  the  bones,  and  may  lead  to  gigantism.  On  the 
other  hand,  inadequate  thyroid  secretion  will  stunt 
the  growth  of  the  bones,  as  is  seen  in  cretinism. 
Thyroid  medication  will  occasionally  lead  to  the 
consolidation  of  an  ununited  fracture,  or,  what  comes 
to  the  same  thing,  the  internal  secretion  of  the 
thyroid  gland  may  be  increased  by  giving  iodide  of 
potassium. 

REFERENCE. 
Macewen. — "The  Growth  of  Bone,"   Glasgow,   1911. 


69 


CHAPTER    V. 

THE    THYROID    AND    PARATHYROID 
GLANDS. 

History — Removal  of  the  thyroid  and  parathyroids — Removal 
of  parathyroids  alone — Removal  of  thyroid  alone — Thyroid 
feeding — Chemistry  of  thyroid  colloid — Parenchymatous  goitre 
— Iodoform  and  thyroidism — Action  of  iodides  on  gummata  and 
atheroma — Exophthalmic  goitre — Practical  deductions. 

MUCH  of  the  clinical  and  experimental  work 
which  has  been  done  in  connection  with 
these  glands  can  no  longer  be  described  as  new,  but 
it  will  be  helpful  to  mention  in  passing  some  of  the 
well-known  results  obtained  by  the  first  observers. 

HISTORY. 

As  long  ago  as  1859,  Schiff  described  the  fatal 
result  which  inevitably  supervenes  after  removal  of 
the  thyroid  gland  in  dogs,  but  it  was  not  until 
'  cachexia  strumipriva,"  or  operative  myxcedema, 
was  found  to  follow  so  many  of  Kocher's  early 
operations  for  goitre  on  patients  coming  from  the 
goitrous  Swiss  valleys,  that  this  fact  attracted  much 
attention.  The  relation  of  the  thyroid  to  myxoedema 
was  then  established  by  Gull  and  Ord.  The  highly 
successful  treatment  of  myxcedema  and  cretinism  by 
thyroid  feeding  was  introduced  by  Murray,  follow- 
ing on  the  observation  by  Schiff  and  subsequent 
workers  that   transplantation  of  the  gland  beneath 


70  THE    THYROID    AND 

the   skin   of    the  thyroidectomized  animal  relieved 
the  symptoms. 

REMOVAL  OF  THYROID  AND  PARATHYROIDS. 

We  will  consider  first  the  consequences  of  removal 
of  the  thyroid  gland  in  animals.  The  effect  of 
total  removal  varies  greatly  with  the  species.  Thus 
rodents  are  little  if  at  all  affected,  sheep  and  cattle 
more  so ;  in  man  and  monkeys  the  symptoms  are 
marked,  and  in  carnivores,  especially  foxes,  a  rapidly 
fatal  result  ensues.  To  some  extent  this  striking 
diversity  depends,  as  we  shall  see,  on  the  liability  to 
simultaneous  removal  of  the  parathyroids ;  for  a 
long  time  this  was  not  recognized.  Males  are  more 
severely  affected  than  females,  and  castration  is 
said  to  modify  the  symptoms.  Thyroidectomized 
animals  are  very  susceptible  to  cold,  and  keeping 
cats  warm  may  save  their  lives ;  of  course  thyroid 
medication  mi  st  be  undertaken  at  the  same  time. 
It  is  well  known  that  human  patients  with  myxcedema 
feel  the  cold  very  much.  The  symptoms  in  dogs 
and  monkeys  are  vomiting,  muscular  prostration, 
emaciation,  and  often  death.  Of  great  importance 
is  the  frequent  occurrence  of  tetany.  The  spasms 
are  at  first  slight,  affecting  the  jaw  muscles,  then 
they  spread  over  the  whole  body  and  may  be  fatal. 
This  condition  has  several  times  followed  a  too 
extensive  removal  of  the  thyroid  in  man,  and  may 
also  occur  in  myxcedema.  Another  symptom 
present  frequently  in  monkeys  is  narrowing  of  the 
palpebral  fissure,  so-called  enophthalmos ;  we  shall 
see    that    administration    of    thyroid    extract    may 


PARATHYROID    GLANDS  71 

cause  exophthalmos.  True  myxcedema  is  not  often 
seen  in  the  experimental  animals.  It  has  been 
induced  in  mild  degree  in  monkeys  by  Horsley, 
Edmunds,  and  others,  but  not  with  any  constancy, 
and  in  other  animals  it  is  not  seen  at  all. 

It  is  not  usually  possible  to  save  the  lives  of  dogs 
or  monkeys  whose  thyroids  have  been  removed, 
by  feeding  on  sheep's  thyroid,  although  a  good  deal 
of  relief  may  be  obtained  for  the  symptoms  in  this 
way.  Grafting  a  piece  of  the  gland  under  the  skin 
is  successful  for  a  while,  but  eventually  it  is  absorbed. 

The  effects  of  removal  of,  or  insufficient  secretion 
by,  the  thyroid  gland  in  man  are  myxcedema,  and 
occasionally  tetany. 

In  408  cases  in  Kocher's  clinic  at  Berne  complete 
extirpation  of  the  thyroid  was  followed  by  myxcedema 
in  69  cases,  and  a  similar  operation  in  78  cases  in 
Billroth' s  clinic  was  followed  by  tetany  in  13  cases, 
of  which  6  proved  fatal.  Feeding  with  sheep's 
thyroid  is  wonderfully  successful  in  myxcedema, 
but  is  not  usually  effectual  in  tetany. 

Partial  removals  of  the  thyroid  in  dogs  produce 
symptoms  of  correspondingly  lessened  severity. 
Halstead  found  that  in  one  case  one-eighteenth  of 
the  gland  sufficed  to  ward  off  symptoms  of 
athyroidism,  but  the  amount  which  could  safely  be 
left  varied  in  different  animals.  One  bitch  which 
had  lost  two-thirds  of  her  total  thyroid  became 
pregnant  by  a  healthy  male,  and  all  her  whelps  had 
enormous  goitres,  a  fact  which  has  also  been 
observed  by  Edmunds. 

Histological  examination  of  the  portion  remaining 


72  THE    THYROID    AND 

shows  a  sequence  of  changes  remarkably  like  those 
occurring  in  exophthalmic  goitre,  namely,  distention 
and  irregular  shape  of  the  vesicles,  with  watery  fluid 
instead  of  colloid,  and  columnar  epithelium  instead 
of  cubical. 

REMOVAL     OF     PARATHYROIDS. 

The  variation  in  the  symptom-complex  following 
on  thyroidectomy,  and  the  variability  of  response 
to  thyroid  feeding,  both  depend  on  any  coincident 
injury  to  the  parathyroid  glands.  For  many  years 
these  glands  passed  unrecognized,  and  most  of  the 
effects  attributed  above  to  removal  of  the  thyroid 
are  as  a  matter  of  fact  due  to  loss  of  the  parathyroids. 
These  are  two  pairs  of  small  glands,  about  one-third 
of  an  inch  long  and  usually  flattened  in  shape,  lying 
behind  the  lateral  lobes  of  the  thyroid  close  to  the 
trachea,  not  easily  distinguishable  from  the  thyroid 
except  by  the  microscope,  when  they  are  seen  to 
consist  of  columns  of  polygonal  cells  with  no  regular 
arrangement  into  acini,  and  secreting  no  colloid. 
One  pair  was  discovered  by  Sandstrom  in  1880, 
and  the  functions  were  investigated  by  Gley  in 
1892  ;  but  the  second  pair  was  not  recognized  till 
Kohn's  monograph  appeared  in  1895.  A  number  of 
physiologists  have  since  described  the  effects  of 
removal  (Vassali  and  Generali,  Edmunds,  Moussu). 
If  all  four  parathyroids  are  taken  away,  the  animal 
succumbs  rapidly,  with  symptoms  just  such  as  have 
been  described  under  the  heading  of  thyroidectomy, 
tetany  being  a  marked  feature.  The  signs  are  the 
same  whether  the  thyroid  gland  is  removed  or  left. 


PARATHYROID    GLANDS  73 

Leaving  one  parathyroid  is  usually  sufficient  to 
prevent  death,  but  tetany  may  still  ensue. 

Changes  in  the  human  parathyroids  are  said  to  be 
very  frequent  in  cases  of  tetany  in  children  or 
pregnant  women,  and  also  in  osteomalacia,  in  which 
the  inorganic  matter  of  bone  is  largely  removed.  In 
fact  it  is  probable  that  the  tetany  itself  depends  on 
some  abnormality  of  the  calcium  metabolism  of  the 
body.  The  main  function  of  the  parathyroid  glands 
is  perhaps  to  control  the  calcium  metabolism. 

It  would  seem  that  in  man,  myxcedema  is  due  to 
loss  of  the  internal  secretion  of  the  thyroid  itself, 
but  that  tetany  and  fatal  symptoms  in  both  man 
and  animals  are  due  to  loss  of  the  parathyroids. 
The  convulsions  of  tetany  in  dogs  may  be  arrested 
by  feeding  on  a  watery  extract  of  twelve  to  twenty 
horses'  parathyroids  (Moussu). 

REMOVAL     OF     THYROID     ALONE. 

Removal  of  the  thyroid  gland  without  the  para- 
thyroids is  usually  not  fatal ;  myxcedema  results 
in  man ;  occasionally,  perhaps,  in  animals  also, 
but  more  commonly  only  cachexia.  In  young 
animals,  however,  the  results  are  much  more  dis- 
tinct, and  Eiselsberg  and  others  have  induced  very 
convincing  cretinism,  with  a  remarkable  stunting 
of  growth,  in  lambs,  goats,  rabbits,  and  asses.  It 
is  interesting  and  important  to  notice  that  the 
animals  so  treated  developed  exceedingly  marked 
atheroma  of  the  aorta,  of  which  Eiselsberg  gives 
good  figures. 


74  THE    THYROID    AND 

THYROID  FEEDING. 
We  now  turn  to  the  effects  of  thyroid  feeding  in 
the  normal  man  and  animal.  These  are  perfectly 
characteristic  if  large  doses  are  given.  The  blood- 
pressure  falls,  the  pulse  becomes  rapid  (120-140  or 
more),  there  may  be  fever,  headache  is  usual,  and 
there  is  great  mental  depression  or  excitement  in 
many  cases.  Exophthalmos  has  been  recorded 
several  times  after  an  overdose  in  man  (Beclere, 
Notthaft),  and  monkeys  (Edmunds).  The  metabolic 
exchanges  of  the  body  are  increased,  consequently 
there  are  loss  of  weight  and  an  increased  output  of 
urea,  chlorides,  and  phosphates,  and  the  gaseous 
exchanges  in  the  lungs  are  above  normal  (Roos, 
Magnus  Levy).  It  will  be  noticed  that  the  parallel- 
ism with  Graves'  disease  is  very  striking. 

CHEMISTRY     OF*    THYROID     COLLOID. 

Chemical  investigation  of  the  colloid  has  yielded 
some  important  results.  The  active  principle, 
iodothyrin,  has  the  characters  of  a  globulin  (Oswald) 
which  contains  a  variable  proportion  of  iodine.  This 
element  is  usually  abundant  in  the  thyroid,  but 
almost  absent  in  the  other  tissues  of  the  body.  Its 
presence  was  first  proved  by  Baumann  of  Freiburg, 
in  1896,  and  has  been  abundantly  confirmed  since. 
The  amount  present  varies  with  the  species  and  also 
with  the  individual ;  in  some  cases  it  falls  below 
the  limits  of  chemical  recognition.  Herbivores 
possess  it  in  abundance,  most  vegetables  containing 
iodine.  In  carnivores  it  is  very  scanty.  In  man  it 
is  nearly  always  present  in  recognizable  quantities, 


PARATHYROID    GLANDS  75 

except  in  young  children.  Wells  finds  that  the 
amount  varies  with  the  locality,  and  in  general  is 
inversely  in  proportion  to  the  local  prevalence  of 
goitre.  In  parenchymatous  goitre  the  iodine  content 
is  too  low  ;  in  exophthalmic  goitre  it  is  too  high.  A 
principal  function  of  the  thyroid  is  to  control  the 
iodine  metabolism  of  the  body. 

PARENCHYMATOUS  GOITRE. 
Directing  our  attention  now  to  enlargements  of 
the  thyroid  gland,  we  rule  out  those  that  are  merely 
due  to  tumour  formation,  such  as  adenoma  or  cystic 
disease,  and  confine  ourselves  to  the  parenchyma- 
tous goitres.  It  has  long  been  known  that  there  is 
some  connection  between  drinking-waters  and  the 
incidence  of  goitre.  The  disease  is  extraordinarily 
prevalent  in  certain  districts,  and  especially  where 
the  water-supply  is  derived  from  particular  geological 
formations,  such  as  the  molasse  in  Switzerland 
and  the  carboniferous  limestone  in  Derbyshire.  In 
Khokand,  Turkestan,  a  very  large  proportion  of  the 
whole  population  suffers,  and  Russian  soldiers 
stationed  there  rapidly  acquire  the  disease.  The 
introduction  of  a  new  water-supply  has  several  times 
induced  an  epidemic  of  goitre  in  a  town,  or,  on  the 
other  hand,  reduced  the  number  of  cases  in  an 
endemic  area.  Thus  at  Rupperswyl,  near  Aarau, 
an  endemic  area  in  which  59  per  cent  of  the 
children  were  goitrous,  in  1884  the  water-supply  was 
changed  for  one  from  a  non-goitrous  district,  and 
in  ten  years  the  percentage  had  fallen  to  eleven. 
There  are  on  the  Continent  certain  goitre  wells  called 


76  THE    THYROID    AND 

Kropfbrunnen,  at  which  young  men  anxious  to 
escape  conscription  drink.  They  have  been  known 
for  centuries,  and  the  water  will  induce  goitre  in 
horses  and  dogs,  as  well  as  in  man.  Boiling  the 
water  destroys  its  remarkable  effect  on  the  thyroid 
gland.  This  has  been  taken  to  prove  that  some 
living  organism  is  the  effective  cause,  but  another 
theory  is  more  probable,  as  we  shall  see  later. 

During  Captain  Cook's  voyage  in  1772,  it  is  related 
that  the  crew  ran  short  of  water,  and  had  recourse  to 
blocks  of  ice  from  the  icebergs  amongst  which  they 
were  sailing,  melting  them  in  iron  pots.  Quite  a 
number  of  those  who  partook  of  this  water  developed 
a  goitre,  other  members  of  the  crew  escaping. 

A  large  projecting  swelling  of  the  thyroid  is  not 
uncommon  in  trout  kept  in  certain  tanks  or  streams. 

In  the  earlier  stages,  parenchymatous  goitre  can 
usually  be  cured,  either  by  feeding  on  thyroid  extract 
or  by  means  of  potassium  iodide.  Marine*  has 
pointed  out  that  in  America  there  was  formerly  a 
serious  commercial  loss  in  some  districts  from  cretin 
lambs,  and  that  sheep  and  dogs  with  goitre  were 
numerous ;  the  substitution  of  an  iodiferous  salt 
for  pure  rock-salt  has  been  completely  successful 
in  preventing  all  these  manifestations. 

Chalmers  Watson,  and  more  recently  Edmunds, 
have  obtained  goitre  in  fowls  by  a  meat  diet.  The 
low  iodine-content  of  the  meat  makes  it  necessary 
for  the  thyroid  to  enlarge,  so  as  to  take  the  greatest 
advantage  of  what  iodine  it  can  get. 

*  Johns  Hopkins  Hosp.  Bull.,  1907,  xviii,  p.  359. 


PARATHYROID    GLANDS  77 

There  is  abundant  evidence  that  iodides,  and 
especially  organic  combinations  of  iodine  such  as 
iodoform,  have  great  power  in  enhancing  the 
activity  of  the  thyroid  gland.  We  have  already 
seen  that  the  gland  normally  secretes  iodine  into  the 
blood-stream,  combined  with  a  globulin.  Roos, 
and  more  recently  Hunt  and  Seidel,  have  shown 
that  the  activity  of  the  colloid  varies  directly  with 
the  amount  of  iodine  contained  in  it.  When  iodides 
or  iodoform  are  given  by  mouth,  they  are  taken  up 
by  the  thyroid  and  secreted  in  the  blood-stream  in 
the  form  of  iodothyrin,  the  normal  active  principle 
of  the  gland.  The  amount  of  iodine  in  the  gland  in 
these  circumstances  rises  considerably,  as  has  been 
proved  by  Oswald  in  man,  and  by  Hunt  and  Seidel 
in  dogs. 

What,  then,  is  the  relation  between  iodine 
metabolism  and  goitre  ? 

In  the  first  place,  we  may  conclude  that  the 
thyroid  enlarges  in  goitre  because  it  is  necessary 
for  it  to  do  increased  work.  A  certain  quantity  of 
iodothyrin  is  needful  for  the  general  well-being  of  the 
individual ;  if  the  gland  is  scantily  supplied  with 
iodine,  it  must  enlarge  in  order  to  take  the  fullest 
possible  advantage  of  all  that  may  be  brought  to 
it  by  the  blood-stream.  In  the  same  way  a  kidney 
hypertrophies  when  its  fellow  is  degenerated,  in  order 
to  obtain  more  urea  for  excretion ;  and  the  red  blood- 
corpuscles  double  in  number  when  a  man  takes  up 
his  abode  in  the  rarefied  atmosphere  of  great  alti- 
tudes, to  make  the  best  use  of  the  diminished  supply 
of  oxygen.     It  has  been  shown  by  Oswald  in  a  number 


78  THE    THYROID    AND 

of  observations  that  in  goitre  the  thyroid  colloid  is 
exceedingly  deficient  in  iodine,  both  in  calves  and 
man.  Thus  we  get  a  clue  to  the  successful  treatment 
of  the  affection  either  by  iodiferous  compounds 
or  by  thyroid  extract.  It  is  well  known  that  either 
of  these  remedies  will  cure  early  cases  of  goitre, 
before  the  enlargement  becomes  chronic.  The 
success  of  the  iodiferous  rock-salt  on  the  American 
farms  may  be  accounted  for  in  the  same  way.  An 
explanation  is  also  offered  of  the  fact,  noticed 
previously,  that  the  whelps  of  bitches  from  whom 
a  good  part  of  the  thyroid  has  been  removed  are 
all  goitrous,  the  plasma  supplied  to  the  foetal  glands 
evidently  containing  a  deficiency  of  iodine  derived 
from  the  maternal  thyroid.  Of  2,333  cases  of  con- 
genital goitre  collected  by  Fabre  and  Thevenot,*  the 
mother  was  almost  invariably  goitrous.  The  foetal 
thyroid  enlarges  in  order  to  obtain  as  much  iodine 
as  it  can. 

It  was  natural  to  suggest  that  the  waters  of  the 
Kropfbrunnen  were  deficient  in  iodine,  but  this 
theory  would  overlook  the  fact  that  the  bulk  of  our 
iodine  is  derived  from  vegetables,  not  from  drinking- 
water,  and  as  a  matter  of  fact  these  wells  show  no 
constant  deficiency  or  excess  of  iodine.  It  is  more 
probable  that  they  contain  minute  traces  of  some 
metal  having  a  great  affinity  for  iodine,  and  forming 
with  it  an  insoluble  compound.  It  is  quite  conceiv- 
able that  boiling  the  water  might  precipitate  such 
a  metal.     There  are  probably  many  metals,  known 

*  Revue  de  Chirurgie,  June  io,  1908. 


PARATHYROID    GLANDS  79 

and  unknown,  that  would  fulfil  the  conditions ;  it 
will  suffice  to  mention  silver  as  an  illustration.  This, 
if  taken  into  the  body,  would  withdraw  so  much  of  the 
available  iodine  as  inert  silver  iodide,  that  the  thyroid 
must  enlarge  to  obtain  the  indispensable  minimum. 

Major  McCarrison,  who  has  been  observing  endemic 
goitre  amongst  the  Gilgit  highlands  in  North  India, 
has  lately  brought  forward  fresh  arguments  in  favour 
of  a  bacteriological  theory  of  its  causation.  He  has 
induced  a  definite  swelling  of  the  thyroid  both  in 
himself  and  in  natives  by  drinking  the  muddy  residue 
on  the  filter  ;  the  filtered  water,  in  a  short  experi- 
ment, did  not  give  rise  to  goitre,  nor  did  boiled  water. 

No  organism  could  be  found  in  punctures  of  the 
gland.  Goats  given  water  to  drink  contaminated  by 
the  faeces  of  goitrous  patients  in  some  cases,  though 
not  in  others,  developed  a  certain  amount  of  swelling 
of  the  thyroid  gland,  and  in  man  ten-grain  doses  of 
thymol,  used  as  an  intestinal  antiseptic,  reduced  the 
size  of  a  goitre  in  some  patients.  Hence,  McCarrison 
believes  that  the  disease  is  due  to  an  intestinal 
organism.  The  evidence  does  not  seem  very  conclu- 
sive ;  chemical  substances  permeating  certain  geo- 
logical formations  we  are  acquainted  with,  but 
pathogenic  bacteria  having  a  special  soil  distribution 
would  be  a  novelty.  According  to  Wilms,  Bircher, 
and  others,*  the  water  of  goitre  wells  retains  the 
power  of  inducing  thyroid  enlargement  in  rats  after 


*  Bircher,  Deut.  med.  Wochensch.,  1910,  No.  37  ;  Wilms,  Deut 
med.  Wochensch.,  1910,  No.  13  ;  Kolle,  Korrespond.  f.  schweiz.. 
Arzte,  1909,  No.  17. 


80  THE    THYROID    AND 

passing  through  a  Berkefeldt  filter.  It  is  true  that 
a  very  few  tiny  bacteria  are  filter-passers,  but  the 
immense  majority  are  held  back.  It  is  easy  to 
cause  enlargement  of  the  thyroid  by  various  means  ; 
Bircher  shows  that  food  contaminated  by  the  faeces 
of  normal  rats  causes  goitre  in  other  rats. 

There  are  goitre  wells  in  England.  One  is  known 
to  the  writer  near  Berkeley,  in  Gloucestershire. 
Its  water  is  used  by  only  one  or  two  families,  but 
four  cases  of  goitre  have  resulted.  It  is  usually  the 
growing  children  who  suffer. 

IODOFORM    AND     THYROIDISM. 

The  conclusions  which  modern  physiology  has 
reached  with  regard  to  the  relation  between  iodine 
compounds  and  the  thyroid  gland  lead  us  to  some 
further  important  explanations  of  obscure  problems. 
We  are  now  able  to  understand  the  toxic  effects  of 
iodoform,  and  the  beneficial  action  of  iodides  on 
arteriosclerosis,  aneurysm,  and  gummata. 

Iodoform  poisoning  has  become  a  well-recognized 
condition,  and  every  text- book  on  pharmacology  or 
toxicology  gives  a  clear  description  of  the  clinical 
picture,  which  the  writer  has  verified  by  consulting 
the  reports  on  some  ioo  cases  scattered  through 
the  literature,  not  including  the  very  numerous 
records  of  dermatitis  or  erythema  following  its  local 
use.  A  long  list  of  well-described  cases  (not  always 
very  convincing)  is  given  by  Cutler.* 

*  Boston  Med.  Soc.  Journal,  1886,  ii:  pp.  73,  101,^110, 


PARATHYROID    GLANDS  81 

There  are  four  main  varieties  of  iodoform  poi- 
soning : — 

1.  Skin  eruptions,  such  as  dermatitis,  erythema, 
and  swelling. 

2.  Persistent  subjective  taste  and  smell  of  the 
drug  long  after  its  application  has  been  discontinued 

3.  Toxic  amblyopia  (5  cases),  and  optic  atrophy 
(1  case). 

4.  Acute  thyroid  symptoms,  comprising  rapid 
pulse,  delirium,  headache,  vomiting,  and  a  variable 
amount  of  fever.  The  most  characteristic  sequence 
is  when  the  pulse  is  very  rapid  but  the  temperature 
normal. 

Of  the  above  groups  we  are  now  concerned  only 
with  the  last. 

It  will  be  noticed  that  the  clinical  picture  cor- 
responds exactly  to  that  seen  after  the  adminis- 
tration of  excessive  doses  of  thyroid  extract.  Iodo- 
form causes  its  toxic  effects  by  stimulating  the 
internal  secretion  of  the  thyroid  gland,  with  the 
production  of  acute  thyroid  intoxication. 

I  have  described  a  case  in  which  chronic  thyroid 
intoxication,  that  is  to  say  Graves'  disease,  clearly 
followed  the  application  of  iodoform  to  an  absorbing 
surface.  There  was  certain  proof  that  too  much 
iodoform  was  absorbed,  because  for  weeks  after  the 
drug  had  been  withdrawn  the  patient  was  haunted 
by  its  smell  and  taste.  The  tachycardia  and  wasting 
were  first  noticed  a  week  or  two  after  this  symptom 
developed.  The  Graves'  disease  was  still  present  in 
a  mild  form  one  year  later,  but  eventually  disappeared. 

Hunt  and  Seidel  have  shown  that  after  dosing 

6 


82  THE    THYROID    AND 

a  dog  with  iodoform,  the  iodine  content  and  the 
activity  of  the  thyroid  colloid  are  both  increased 
greatly.  The  thyroid  secretes  into  the  blood,  as 
iodothyrin,  the  iodine  derived  from  the  iodoform. 
When  strychnine  is  excreted  by  the  kidneys  the 
excretion  is  merely  discharged  from  the  body,  and 
therefore  the  drug  can  do  no  more  harm.  But  the 
increased  secretion  of  the  thyroid  is  discharged  not 
externally  but  into  the  blood,  and  may  poison  the 
patient. 

ACTION     OF     IODIDES     ON     GUMMATA     AND 
ATHEROMA. 

A  similar  increase  in  the  thyroid  secretion  may 
be  obtained  by  giving  iodides,  but  apparently  the 
gland  is  not  able  to  utilize  these  as  readily  as  it  does 
iodoform,  for  large  doses  do  not  so  easily  cause 
acute  thyroid  intoxication.  Here  we  find  the  ex- 
planation, so  long  sought  Li  vain,  of  the  effect  of 
iodides  on  gummata,  arteriosclerosis,  and  aneurysm. 
The  beneficial  agent  is  really  the  increased  internal 
secretion  of  the  thyroid  gland. 

Two  important  results  of  observation  and  experi- 
ment confirm  this  theory. 

In  the  first  place,  in  cases  of  myxcedema,  arterio- 
sclerosis is  early  and  intense.  The  same  is  true  in 
animals  after  removal  of  the  thyroid.  Eiselsberg 
gives  a  number  of  very  convincing  photographs  of 
intense  atheroma  of  the  aorta  in  his  cretin  lambs 
in  which  the  thyroid  had  been  removed  in  early  life. 
In  the  second  place,  thyroid  extract  has  a  wonderful 
power  over  young  connective  tissue,  as  is  seen  by  the 


PARATHYROID    GLANDS  83 

way  in  which  it  absorbs  the  subcutaneous  thickening 
of  myxcedema  and  cretinism.  It  is  not  surprising, 
therefore,  that  it  should  be  able  to  deal  also  with 
gummata  and  atheroma.  By  its  absorptive  effect 
on  the  atheroma,  it  may  work  some  improvement  in 
aneurysm. 

I  have  found  thyroid  extract  quite  as  effectual  as 
iodide  of  potassium  in  healing  tertiary  syphilitic 
ulcers. 

EXOPHTHALMIC     GOITRE. 

The  arguments  in  favour  of  the  hypersecretion 
theory  of  this  disease  appear  to  almost  all  observers 
to  be  of  overwhelming  strength.  The  thyroid 
gland  is  enlarged,  vascular,  and  soft  in  most  cases ; 
occasionally  it  is  normal  in  size.  Microscopically, 
the  acini  are  dilated  and  irregular,  and  the  contents 
too  watery.  These  are  just  the  changes  seen  in  the 
actively  secreting  fragment  left  after  a  sub-total 
thyroidectomy.  The  colloid  contains  too  much 
iodothyrin  as  compared  with  the  normal  gland. 
The  wasting,  restlessness,  and  quick  pulse  may  all 
be  reproduced  with  constancy  in  man  or  animals 
by  thyroid  feeding,  and  exophthalmos  has  also  been 
obtained  occasionally  in  both  man  and  the  monkey. 
The  underlying  cause  of  the  hypersecretion  is  still 
unknown.  A  few  cases  may  be  lighted  up  by  fright 
or  by  iodoform  poisoning. 

PRACTICAL     DEDUCTIONS. 

We  may  seek  here  to  summarize  the  conclusions, 
in  so  far  as  they  are  of  importance  to  the  clinician, 


84  THE    THYROID    AND 

that  the  New  Physiology  has  reached.  We  learn 
that  parenchymatous  goitre  is  an  hypertrophy  of 
the  thyroid  gland,  designed  to  enable  it  to  obtain 
sufficient  iodine  from  the  blood,  this  element  being 
an  essential  constituent  of  its  internal  secretion. 
The  deficiency  in  iodine  is  in  some  complicated  way 
connected  with  the  drinking-water.  In  the  early 
stages,  iodides,  thyroid  feeding,  or  probably  iodo- 
form will  work  improvement,  and  the  water  should 
be  boiled,  or  the  supply  changed.  Should  operative 
measures  be  adopted,  we  learn  that  the  whole  gland 
must  not  be  removed,  or  myxcedema  may  result, 
and  that  the  four  small  parathyroids  lying  behind 
it  must  also  be  respected,  or  the  patient  may  develop 
tetany.  In  some  cases  the  loss  of  the  parathyroids 
on  one  side  only  has  caused  this  unpleasant  sequel. 
An  attempt  should  therefore  be  made,  in  removing 
one  lobe  of  the  thyroid  for  goitre  or  adenomata,  to 
leave  these  little  glands  intact  and  in  situ,  and  to 
preserve  their  blood-supply.  They  will  not  be 
injured  if  the  posterior  part  of  the  capsule  of  the 
thyroid  is  left. 

If  myxoedema  or  tetany  do  follow  the  operation, 
they  may  be  remedied  by  thyroid  and  parathyroid 
feeding  respectively.  There  is  some  evidence  that 
even  the  medical  varieties  of  tetany  are  due  to  loss  of 
the  internal  secretion  of  the  parathyroids  ;  according 
to  Kocher,  this  has  been  proved  in  the  case  of  the 
tetany  of  pregnancy,  and  other  observations  have 
since  been  made  in  which  the  parathyroids  were 
diseased  when  tetany  was  present.  Parathyroid 
feeding  should  therefore  be  worth  a  trial  in  such 


PARATHYROID    GLANDS  85 

cases  also.  Macallum*  recommends  the  adminis- 
tration of  calcium  salts,  or  milk,  which  is  rich  in 
calcium  salts.  He  has  shown  experimentally,  and 
Edmunds f  has  confirmed  the  statement,  that  these 
salts  will  cure  tetany.  Thyroid  and  parathyroid 
grafting  have  both  been  undertaken  in  man  for 
cretinism  and  tetany  respectively,  with  the  idea  of 
relieving  the  patient  from  the  necessity  of  taking 
drugs  all  his  days.  In  a  few  cases  success  has 
resulted,  but  unfortunately  the  graft  becomes 
absorbed  as  a  general  rule,  and  soon  ceases  to 
function. 

In  a  case  recently  described  by  Brown,  of 
Melbourne,  parathyroid  feeding  and  calcium  salts 
both  failed  to  relieve  tetany  in  a  patient  who  had 
been  treated  by  a  too  extensive  thyroidectomy  for 
Graves'  disease.  The  in-grafting  of  parathyroid 
tissue  from  dogs  and  monkeys  gave  pronounced  relief 
for  about  twelve  days,  but  she  relapsed  after  each 
operation.  Human  parathyroid  was  then  grafted, 
and  the  cure  seemed  to  be  permanent.  I  have  seen 
a  case  apparently  cured  by  the  grafting  of  human 
parathyroid. 

We  see  also  that  exophthalmic  goitre  is  due  to 
hypersecretion  of  the  iodothyrin,  as  is  proved  by 
the  artificial  imitation  of  the  disease  by  excessive 
thyroid  feeding,  by  the  excess  of  iodine  present  in 
the  colloid  in  Graves'  disease,  and  by  the  character 
of  the  histological  changes.     Thus  we  have  reason 

*  Journal  of  Experimental  Med.,  New  York,  1909,  vol.  xi,  p.  118. 
t  Journal  of  Path,  and  Bad.,  19 10,  p.  288. 


86  THE    THYROID    AND 

to  expect  good  from  partial  removal,  which  has  been 
very  successful  in  the  hands  of  Kocher,  the  Mayos, 
and  others.  It  would  be  reasonable  also  to  try  the 
effect  of  iodine  starvation,  by  eliminating  vegetables 
and  ordinary  tap-water  from  the  dietary,  and  sub- 
stituting for  the  latter  the  water  of  a  goitre  well.  It 
is  well  known  that  exophthalmic  goitre  and  parenchy- 
matous goitre  show  a  sort  of  geographical  antagonism, 
and  the  effect  of  the  water  in  reducing  the  amount  of 
iodine  available  for  conversion  into  iodothyrin  would 
be  valuable. 

Further,  we  are  helped  to  understand  and  to 
recognize  cases  of  iodoform  poisoning,  and  to  learn 
caution  in  the  use  of  this  drug  on  absorbing 
surfaces.  It  is  safer  in  children  than  in  adults, 
possibly  because  the  thyroid  in  children  contains 
less  iodine.  It  ought  not  to  be  used  in  patients 
who  have  ever  shown  a  tendency  to  thyroidism, 
lest  acute  poisoning  or  an  attack  of  Graves'  disease 
be  precipitated. 

Finally,  we  obtain  a  clue  at  last  to  the  remarkable 
action  of  iodides  in  arteriosclerosis  and  gummata, 
and  it  is  reasonable  to  hope  that  organic  compounds 
of  iodine,  which  cause  acute  thyroidism  more  readily 
than  the  alkaline  salts,  may  be  yet  more  effectual 
in  stimulating  the  activity  of  the  thyroid  gland.  In 
fact,  thyroid  extract  itself  may  prove  to  be  the 
best  remedy  of  all. 

Seeing  that  the  activity  of  thyroid  extracts 
depends  only  on  the  iodothyrin,  these  should  be 
standardized  chemically  if  they  are  to  be  given 
as  drugs.      Leading  chemists  now  issue  an  extract 


PARATHYROID    GLANDS  87 

which  contains  not  less  than  0*2  per  cent  organic 
iodine. 

REFERENCES. 

Richardson. — "  The  Thyroid  and  Parathyroid  Glands," 
Philadelphia,  1905. 

Allbutt's  System  of  Medicine,  vol.  iv,  part.  1,  p.  333, 
1907  Edition  (a  full  bibliography). 

Hunt  and  Seidel. — "  Studies  on  Thyroid,"  Hygienic  Labor- 
atory Bulletin  of  Public  Health,  Washington,  1909. 

A.  Rendle  Short. — Bristol  Medico -Chirurgical  Journal, 
1910,  p.   122. 

Kocher,  Hector  Mackenzie. — "  Discussion  on  Exoph- 
thalmic Goitre,"  Brit.  Med.  Journal,  1910,  vol.  ii,  pp. 
931*  935- 

McCarrison. — "  Milroy  Lectures,"  Lancet,   1913,  i. 


83 


CHAPTER    VI. 
THE  PITUITARY  AND   PINEAL  GLANDS. 

The  effects  of  removal  in  animals — Injection  of  extracts — 
Pituitary  feeding — Acromegaly  and  gigantism — Frohlich's  type 
— Functions  of  the  pituitary  gland — Therapeutic  value  of  pituitary 
extract — The  pineal  gland. 

IT  will  be  remembered  that  the  pituitary  gland  is 
lodged  in  the  sella  turcica  of  the  cranium,  in  an 
exceedingly  secluded  position  in  the  body,  and  it  is 
only  recently  that  its  functions  have  been  recognized. 
It  may  be  that  the  interesting  researches  of  Schafer, 
Paulesco,  Cushing,  and  others,  will  prove  to  have 
opened  up  a  very  important  and  useful  chapter  in 
medicine  as  well  as  in  physiology. 

The  gland  consists  of  two  distinct  portions,  anterior 
and  posterior,  closely  fused  in  man,  but  with  a  well- 
marked  line  of  junction  in  the  dog.  The  anterior 
part  is  glandular  in  structure,  consisting  of  columns 
of  epithelial  cells  which  generally  contain  colloid. 
In  young  animals  these  cells  line  tubules  ;  later, 
the  central  lumen  disappears.  Large  blood  sinuses 
are  present.  The  posterior  lobe  consists  of  vascular 
neuroglia.  Between  it  and  the  anterior  lobe  is  a 
cleft  containing  glairy  fluid.  The  anterior  portion 
is  derived  from  a  pit  in  the  dorsal  wall  of  the  pharynx 
of  the  embryo  ;  the  posterior  is  budded  out  from 
the    brain. 


PITUITARY    AND    PINEAL    GLANDS      89 

All  the  ductless  glands  are  studied  by  four  methods. 
We  have  to  find  the  effects,  firstly,  of  removal  in 
animals  ;  and  secondly,  of  the  injection  or  ingestion 
of  extracts.  We  have,  thirdly,  to  make  chemical 
analyses  of  the  extracts,  to  isolate  any  active  principle. 
Finally,  a  clinical  study  of  symptoms  in  man  associ- 
ated with  any  abnormalities  of  the  gland  may  be 
expected  to  throw  a  light  on  the  problem,  and  the 
effect  of  treating  these  conditions  will  also  need  to 
be  known. 

These  are  here  set  forth  in  the  rational,  not  in 
the  historical  order.  It  may  be  said  at  once  that 
the  active  principle  or  principles  have  not  yet  been 
isolated. 


THE    EFFECTS    OF    REMOVAL    OF    THE 
PITUITARY    GLAND    IN     ANIMALS. 

It  is  so  difficult  to  remove  the  organ  from  its  well- 
concealed  nest  that  the  earlier  published  results 
inspired  no  confidence.  It  was  said  that  the  animals 
died,  but  the  injury  to  vital  structures  was  necessarily 
great,  and  it  has  been  remarked  that  the  result 
would  probably  have  been  equally  fatal  if  the 
operator  had  removed  the  dorsum  sellae  instead  of  the 
gland  !  But  the  careful  and  repeated  observations 
of  Paulesco  on  twenty-two  animals,  and  of  Gushing 
and  his  co-workers  on  about  two  hundred  dogs, 
have  completely  established  confidence  in  the  state- 
ments now  before  us. 

It  is  proved  that  removal  of  the  anterior  lobe  alone, 
in  dogs,  produces  just  as  much  effect  as  removal  of 


90  THE    PITUITARY    AND 

the  whole  gland,  but  that  a  removal  limited  to  the 
posterior  lobe  causes  no  symptoms  at  all. 

The  animal,  after  a  total  removal,  shows  no 
deviation  from  the  normal  for  a  period  varying  from 
thirty-six  hours  to  two  weeks  after  the  operation. 
Then  it  becomes  unsteady,  there  are  arching  of 
the  back,  low  temperature,  shivering,  and  death 
in  unconsciousness.  Achsner,  Handelsmann  and 
Horsley,  Morawski  and  others,  however,  find  that 
death  is  by  no  means  inevitable  after  enucleation 
either  of  the  anterior  lobe  or  the  whole  gland,  and 
positive  evidence  of  survivals  must  outweigh  state- 
ments to  the  contrary. 

Cushing  has  found  it  possible  to  effect  partial 
removals  of  the  gland.  In  young  animals,  the  result 
is  that  an  "  infantile  "  type  is  maintained,  and  the 
secondary  sexual  characters  do  not  develop.  In 
older  animals,  the  genitals  atrophy,  and  they  get  very 
fat.  He  gives  very  convincing  photographs  showing 
that  these  changes  are  quite  marked. 

Another  consequence  is  a  remarkable  influence 
upon  the  metabolism  of  sugar.  We  shall  see  that 
removal  of  the  pancreas  causes  glycosuria.  Partial 
removal  of  the  pituitary,  on  the  other  hand,  causes  an 
increased  power  of  warehousing  sugar  in  the  body. 
In  man,  if  more  than  150  grams  of  glucose  are 
taken  at  a  dose,  some  will  overflow  in  the  urine.  If 
the  action  of  the  pituitary  was  subnormal,  judging 
by  the  results  of  animal  experiments  and  a  few 
observations  on  man,  even  a  larger  dose  than  this 
would  not  cause  glycosuria. 


PINEAL    GLANDS  91 

INJECTION  OF  EXTRACTS  OF  PITUITARY  GLAND. 
PITUITARY    FEEDING. 

Injection  of  extracts  of  the  anterior  lobe  causes 
no  evident  results.  Injection  of  extracts  of  the 
posterior  or  nervous  lobe  causes  quite  constantly  a 
prolonged  rise  of  blood-pressure.  Not  only  the  blood- 
vessels, but  all  varieties  of  unstriped  muscle  are 
stimulated  to  contract.  Peristaltic  movements  are 
set  up  in  the  bowel,  and  the  bladder  and  uterus, 
whether  pregnant  or  not,  also  contract. 

Prolonged  pituitary  feeding  in  animals  leads  to 
great  emaciation.  It  was  originally  stated  by 
Schafer  that  young  rats  showed  an  exaggeration  of 
growth  when  fed  with  this  gland,  but  repetition  of 
the  experiment  by  himself  and  others  does  not  con- 
firm this. 

Pituitary  extract  also  stimulates  the  secretion  of 
milk  in  animals,  but  it  is  not  yet  proven  that  it  does 
so  in  the  human  subject. 

CLINICAL     RESULTS     OF    LESIONS    OF    THE 
PITUITARY     GLAND. 

It  is  well  known  that  the  somewhat  rare  diseases 
acromegaly  and  gigantism  are  generally  but  not 
quite  invariably  associated  with  enlargement  of 
the  pituitary  gland,  which  has  usually  been  a  simple 
overgrowth,  although  later  adenoma  or  fibrosis  may 
have  developed.  Whether  acromegaly  or  gigantism 
will  result  appears  to  be  principally  a  question  of 
the  age  at  which  symptoms  commence.  If  they 
have  their  onset  before  growth  ceases,  gigantism  will 
result.     The  skulls  of  most  of  the  classical  cases  of 


92  THE    PITUITARY    AND 

gigantism,  including  Patrick  O'Byrne,  Hunter's 
famous  giant,  and  Patrick  Cotter,  the  Bristol  giant, 
have  enormous  sellae  turcicae  to  accommodate  the 
enlarged  pituitary  gland.  It  is  probable  that  giants 
usually  suffer  from  acromegaly  as  well.  There  are  two 
authentic  casts  preserved  in  Bristol  of  Patrick  Cotter's 
hand,  one  of  which  is  much  larger  than  the  other; 
indeed,  it  is  colossal,  measuring  12  inches  from  wrist 
to  finger-tips,  whereas  the  earlier  cast  measures  only 
11  inches.  His  shoes,  which  are  also  preserved,  are 
15  inches  long.  It  is  therefore  clear  that  although 
he  was  7  ft.  10  in.  high,  his  hands  and  feet  were  large 
out  of  all  proportion,  and  that  the  hand  rapidly 
increased  in  size  between  the  taking  of  the  first 
and  second  casts.  The  lower  jaw  was  enormous, 
and  out  of  all  relation  to  the  rest  of  the  skull.* 
Cushing  gives  some  striking  photographs  of  a  living 
giant,  8  ft.  3  in.  high,  showing  enormous  hands 
and  feet. 

Associated  with  the  enlarged  bones  of  the  face, 
hands,  and  feet  seen  in  acromegaly,  there  are  in  some 
cases  other  features  ;  these  are  glycosuria,  amenor- 
rhea, impotence,  and,  in  the  young,  failure  of  the 
secondary  sexual  characters.  The  temperature  is 
subnormal.  This  train  of  symptoms  will  recall  the 
effects  of  total  or  partial  removal  of  the  gland  in 
animals. 

Not  only  the  bones,  but  also  the  viscera,  may  be 
increased  in  size  in  acromegaly  :    the  kidneys,  liver, 


*  E.   Fawcett,  Jour.  Royal  Anthropological  Institute,   1909,   vol. 
xxxix.  p.  196. 


PINEAL    GLANDS  93 

pancreas,  and  even  the  auriculo-ventricular  bundle  of 
the  heart. 

Frohlich  and  others  have  shown  that  there  is 
another  group  of  cases,  totally  distinct  from  acro- 
megaly, but  again  associated  with  tumours  of  the 
pituitary  gland.  These  are  characterized  by  excessive 
fatness,  by  infantile  stature  and  development,  by  a 
childish  type  of  the  genital  organs,  and  by  absence 
of  the  secondary  sexual  characters.  It  may  be  that 
we  shall  yet  find  abnormalities  of  the  pituitary  gland 
in  other  varieties  of  infantilism  or  of  adiposity. 

Most  cases  of  pituitary  tumour  which  have  been 
diagnosed  during  life  have  given  additional  evidence 
of  their  presence  by  involving  the  optic  chiasma  and 
causing  blindness  of  the  nasal  half  of  each  retina. 
The  skiagram  shows  enlargement  of  the  sella  turcica. 
In  many  cases  there  are  headache,  vomiting,  and 
other  signs  of  intracranial  pressure. 

We  must  now  attempt  to  classify  our  information, 
and  endeavour  to  come  to  some  clear  conception  of 
the  functions  of  the  pituitary  gland,  and  the  causa- 
tion of  these  various  types  of  disease. 

A  year  or  two  ago  it  was  the  prevalent  opinion 
that  the  anterior  and  posterior  lobes  must  be  con- 
sidered to  be  entirely  unconnected  glands,  having  a 
different  development,  histology,  and  function.  The 
posterior  lobe  was  connected  with  the  production  of 
an  internal  secretion,  probably  in  the  colloid  fur- 
nished by  the  pars  intermedia,  which  was  poured 
into  the  ventricular  system  of  the  brain,  and  extracts 
of  this  lobe  raised  the  blood-pressure.  There  is  some 
evidence   that   in   acromegaly  the   anterior   lobe   is 


94  THE    PITUITARY    AND 

specially  at  fault ;  it  may  be  disproportionately 
enlarged,  and  may  show  a  superabundance  of  secre- 
tion granules. 

Now,  however,  there  is  a  tendency  to  unify  the 
functions  of  the  hypophysis  ;  and  to  regard  it  as  one 
gland,  although  the  distribution  of  the  colloid  is 
unequal  in  the  various  parts. 

Whether  the  gland  is  necessary  to  life  is  unsettled  ; 
probably  it  is  not. 

The  diseases  fall  into  two  groups  :  those  in  which 
the  internal  secretion  is  excessive  (hyperpituitism), 
and  those  in  which  it  is  diminished  or  absent  (hypo- 
pituitism) . 

Hyperpituitism  is  characterized  by  signs  of  acrome- 
galy in  adults,  or  gigantism  if  it  begins  before  growth 
has  ceased.  The  gland  is  usually  enlarged,  showing 
microscopically  a  simple  overgrowth.  There  may 
be  glycosuria.  The  cases  run  a  chronic  course  for 
years  unless  symptoms  of  cerebral  compression 
come  on. 

Hypopituitism  produces  the  Frohlich  type,  with 
atrophy  of  the  genitals,  infantilism,  and  excessive 
fatness.  There  is  often  a  drowsy  mental  state ; 
indeed,  one  is  tempted  to  believe  that  that  very 
accurate  observer,  Charles  Dickens,  must  have  had 
such  a  case  in  mind  when  he  invented  the  immortal 
Fat  Boy  in  Pickwick.  All  these  symptoms  can  be 
mimicked  by  partial  excisions  of  the  pituitary  gland 
in  animals.  Cushing's  results  as  to  which  lobe  is  at 
fault  are  discordant. 

It  is  true  that  cases  of  acromegaly  may  eventually 
develop  impotence,  sterility,  and  amenorrhcea  ;   this 


PINEAL    GLANDS  95 

is  explained  as  hypopituitism  succeeding  an  excess. 
The  same  alternation  is  seen  in  diseases  of  the  thyroid 
gland. 

A  very  valuable  measure  of  the  function  of  the 
pituitary  gland  may  be  obtained  by  observations  on 
the  power  of  warehousing  sugar.  If  the  internal 
secretion  is  deficient,  huge  quantities  of  glucose  will 
not  cause  glycosuria.  This  is  the  cause  of  the  adipo- 
sity. Hypopituitism  is  usually  due  to  malignant 
growths  encroaching  on  the  gland,  and  is  frequently 
followed  by  death. 

We  are  now  in  possession  of  some  indications  for 
treatment.  Acromegaly  and  gigantism  do  not  usu- 
ally require  anything  to  be  done.  Pituitary  feeding 
does  more  harm  than  good.  If  there  are  symptoms 
of  cerebral  compression  or  gradually  increasing  blind- 
ness from  involvement  of  the  optic  chiasm  a,  an 
operation  may  be  performed  to  relieve  pressure  and 
remove  part  of  the  gland.  Scores  of  cases  have  now 
been  treated  in  this  way  (Cushing  reports  43  operated 
on  by  himself),  and  the  mortality  is  not  high.  Several 
observers  record  a  definite  shrinkage  of  the  bones 
afterwards. 

Patients  suffering  from  the  Frohlich  type  may  be 
treated  by  pituitary  feeding,  the  whole  gland  of 
cattle  being  used.  The  dose  is  about  12  grains  a  day. 
This  may  be  worked  out  by  its  influence  on  the  sugar 
tolerance.  Remarkable  results  have  been  obtained 
in  a  few  cases.  If  there  are  signs  of  intracranial 
pressure  a  decompression  operation  is  indicated. 

The  hope  that  pituitary  feeding  would  prove  to  be 
a  remedy  for  increasing  the  stature  of  small  children 


96  THE    PITUITARY    AND 

is  not  likely  to  be  realized  in  view  of  the  fact  that 
Schafer  has  failed  to  verify  his  earlier  observations 
on  young  rats. 

THE    USES    OF    PITUITARY     EXTRACT. 

Pituitary  extract,  containing  the  principle  found 
in  the  posterior  lobe  which  acts  on  unstriped  muscle, 
is  now  an  ordinary  article  of  commerce  for  many 
therapeutic  purposes.  It  is  a  favourite  remedy  for 
surgical  and  toxsemic  shock,  and  many  observers  are 
convinced  that  it  does  good  by  raising  the  blood- 
pressure.  A  very  valuable  effect  is  that  it  promotes 
peristalsis  even  when  purgatives  fail  or  are  vomited, 
as  in  cases  of  intestinal  paralysis  after  abdominal 
operations.  A  third  indication  is  to  increase  labour 
pains  ;  sometimes  in  cases  of  weak  pains  the  child  is 
expelled  very  rapidly  after  an  injection.  It  is  a 
powerful  diuretic.  As  a  galactagogue  its  success  so 
far  has  been  doubtful.  Feeding  with  the  gland  may 
be  valuable  in  some  forms  of  amenorrhcea. 

Pituitary  extract  must  not  be  given  frequently  at 
short  intervals,  or  its  effect  may  be  reversed. 

THE     PINEAL     GLAND. 

It  has  been  customary  to  look  upon  the  pineal 
gland  as  a  developmental  relic.  The  functionless 
unpaired  eye  of  Hatteria,  which  appears  to  have  been 
present,  possibly  in  functional  form,  in  some  fossil 
reptiles,  is  supposed  to  be  the  substance  of  which  the 
pineal  gland  is  the  useless  shadow.  It  would  be 
truly  extraordinary  if  we  had  to  believe  that  a  super- 
fluous relic  had  been  handed  down  from  the  beginning 


PINEAL    GLANDS  97 

of  the  Triassic  period,  throughout  the  whole  family 
of  the  Mammalia,  and  still  persist  in  man. 

Some  evidence  has  lately  come  to  light  which 
would  lead  us  to  add  the  pineal  to  the  list  of  glands 
with  an  internal  secretion.  It  is  true  that  excision, 
feeding,  and  injection  of  extracts  throw  no  light  on 
the  problem  ;  but  histology  shows  that  it  contains 
in  children  glandular  cells,  which  more  or  less  atrophy 
in  adults.  Tumour  of  the  pineal  gland,  in  about  a 
dozen  recorded  cases,  has  been  associated  with  a 
remarkable  precocity,  including  increased  stature, 
premature  development  of  the  genital  organs,  growth 
of  hair,  and,  in  a  few  instances,  an  extraordinary 
mental  vigour.  One  boy,  at  the  age  of  five,  dis- 
coursed learnedly  concerning  the  immortality  of  the 
soul  ! 

REFERENCES. 

Ojshing. — "The  Pituitary  Gland  and  its  Disorders/'  rgn. 
Biedl. — ■"  The  Internal  Secretory  Organs,"    1913. 
Kidd. — Med.  Chron.,  1912,  vol.  xxiv,  p.  154. 


98 


CHAPTER    VII. 

STUDIES    IN 
THE     CLINICAL    PHYSIOLOGY    OF    THE 
ALIMENTARY    CANAL. 

Movements  of  digestion — Sensation  in  the  alimentary  canal — Causes 
of  variations  in  the  hydrochloric  acid  of  gastric  juice — The 
physiological  effects  of  gastrojejunostomy — Feeding  after  gastros- 
tomy— The  process  of  secretion  of  pancreatic  juice — The  bile — 
The  absorption  of  proteins— Absorption  in  the  large  intestine — 
The  value  of  nutrient  enemata. 

WE  shall  not  repeat  here  the  now  well-known 
researches  of  Pawlow  and  Edkins,  described 
in  our  previous  editions,  showing  the  importance  of 
two  factors  in  provoking  a  flow  of  gastric  juice :  the 
first  the  appetite  reflex  through  the  vagus,  and  the 
second  due  to  the  production  of  gastric  secretin  by 
various  extractives. 

THE     MOVEMENTS     OF     DIGESTION. 

Very  important  and  far-reaching  advances  in  our 
knowledge  of  the  movements  of  various  parts  of  the 
alimentary  canal  have  been  made  by  the  introduction 
of  the  method  of  skiagraphy,  or  direct  observation 
with  the  fluorescent  screen  after  feeding  men  or 
animals  on  milk,  mush,  or  other  food  impregnated 
with  bismuth  salts.  For  this  purpose  the  subnitrate 
should  be  avoided,  as  it  has  led  to  nitrite  poisoning 
when  large  doses  are  given.     Barium  sulphate  is  now 


THE    ALIMENTARY    CANAL  99 

replacing  bismuth  salts  to  some  extent.  The  great 
advantage  of  the  method  is  that  it  is  absolutely 
physiological ;  no  pain  is  caused,  no  operation  is 
needed,  and  permanent  records  can  be  obtained  by 
photography.  Cannon  in  America,  and  Hertz  in 
England,  have  contributed  most  to  our  knowledge 
in  this  field  of  study.  The  bismuth  can  be  given  by 
mouth  or  per  rectum. 

Movements  of  the  CEsophagus  may  be  dis- 
missed in  a  few  words,  as  the  clinical  importance  is 
not  great.  It  is  found  that  the  mere  contraction  ol 
the  pharyngeal  muscles  is  able  to  shoot  fluids  a  long 
way  down  the  oesophagus,  quite  apart  irom  any 
contraction  of  that  tube.  When  corrosives  are 
swallowed,  the  upper  part  of  the  oesophagus  may 
therefore  escape  injury. 

The  peristaltic  wave  in  the  gullet,  unlike  that 
in  the  small  intestine  and  stomach,  is  dependent  on 
a  succession  of  impulses  arriving  from  successive 
nerve-cells  in  the  vagus  nuclei,  whereby  segment 
after  segment  is  led  to  contract  in  regular  order  from 
above  downwards.  In  man,  the  wave  takes  about 
six  seconds,  from  the  first  contraction  of  the  pharynx 
to  the  opening  of  the  sphincter  at  the  cardiac  orifice 
of  the  stomach.  This  sphincter  is  relaxed  by  vagus 
influence. 

If  the  vagi  are  cut,  the  oesophagus  is  paralysed  for 
some  days.  After  a  little  time,  however,  the  muscle 
recovers,  and  peristaltic  waves  can  pass,  so  that 
swallowing  is  once  more  possible. 

The  cardiac  orifice  is  maintained  closed  by  a 
chemical  reflex ;    the  acid  in  the  stomach  causes  a 


100    STUDIES   IN    CLINICAL   PHYSIOLOGY 

spasmodic  contraction  of  the  sphincter  which  is 
relaxed  only  during  swallowing,  vomiting,  or  eructa- 
tion of  gas  or  fluid. 

Shape,  Position,  and  Movements  of  the 
Stomach. — The  stomach  consists  of  two  distinct  parts, 
which  behave  quite  differently  during  digestion.  The 
cardiac  end  and  the  greater  part  of  the  body  form 
an  oval  reservoir  lying  vertically,  with  a  well-marked 
angular  ring  separating  it  off  from  the  horizontal  or 
ascending  narrow  tubular  pyloric  antrum.  After 
death,  or  under  an  anaesthetic,  this  distinction  is  lost, 
but  it  is  often  seen  in  formalin-hardened  bodies. 
Just  after  a  meal,  the  greater  curvature  forms  the 
lowest  point,  and  in  men  while  standing  it  falls  a 
few  centimetres  below  the  umbilicus.  Later,  as  the 
stomach  shortens,  the  pylorus  becomes  the  lowest 
point. 

After  an  ordinary  meal,  movements  of  peristalsis 
start,  usually  about  the  middle  of  the  cardiac  reser- 
voir, and  advance  in  regular  waves  towards  the 
pylorus,  which  remains  tightly  closed.  In  man,  the 
waves  are  about  three  to  the  minute,  and  keep  on  so 
long  as  there  is  food  present.  The  consequence  is 
that  the  gastric  contents  become  thoroughly  mixed 
with  the  digestive  juices.  After  a  while,  when 
these  contents  are  sufficiently  acid,  the  pylorus 
begins  to  yield  momentarily  at  intervals,  and  to  let 
the  food  through  into  the  duodenum.  Whilst  acid 
is  present  on  the  far  side,  the  sphincter  remains 
closed  ;  when  it  is  neutralized  it  opens  again.  Thus 
acid  in  the  stomach  opens  the  pylorus ;  acid  in 
the   duodenum   closes  it.     This   goes    on    until  the 


OF    THE    ALIMENTARY    CANAL       101 

stomach  is  empty.  Even  then  peristalsis  may  not 
cease  (Hertz),  but  the  pylorus  lies  open,  and  bile  and 
duodenal  contents  pass  in  and  out  without  causing 
any  discomfort. 

The  effect  of  the  principal  food-stuffs  on  these 
movements  must  now  be  noticed.  Water  runs  out 
at  the  pylorus  almost  as  quickly  as  it  enters  by  the 
cardiac  orifice.  The  clotting  of  milk  is  probably 
designed  to  prevent  the  same  thing  happening, 
otherwise  it  would  run  through  the  stomach  and 
duodenum  without  giving  the  pepsin  and  trypsin 
time  to  act  upon  it.  Carbohydrates  do  not  stay 
long  in  the  stomach  ;  fats  and  proteins,  however, 
may  remain  for  several  hours.  In  a  normal  human 
stomach,  nothing  should  be  present  before  breakfast 
in  the  morning ;  if  there  is,  some  stasis  must  be 
occurring. 

Emotion  hinders  peristalsis.  Excitable  cats, 
especially  males,  often  show  no  movements  for  a 
long  time  after  being  tied  down ;  Cannon  did  most 
of  his  work  with  placid  elderly  female  cats.  Fever, 
such  as  distemper  in  dogs,  also  diminishes  the  move- 
ments ;  in  fact  food  may  lie  all  day  without  moving. 
There  is  great  delay  after  abdominal  operations.  If 
the  jejunum  is  cut  across  near  the  upper  end  and 
then  sutured,  the  pylorus  remains  tightly  closed  for 
about  six  hours,  even  if  food  is  given. 

Solid  pellets,  such  as  bismuth  pills  or  lead  shot,  are 
not  allowed  to  escape  readily,  and  a  bread  mixture, 
which  usually  began  to  pass  out  into  the  duodenum 
in  fifteen  minutes,  was  retained  for  forty  minutes 
when  the  pills  were  given  with  it.     This  probably 


102    STUDIES   IN   CLINICAL   PHYSIOLOGY 

occurs  when  hard  indigestible  articles  are  taken  as 
food,  and  the  powerful  peristalsis  against  a  spas- 
modically contracted  pylorus  causes  pain. 

Hyperchlorhydria  in  animals  induces  prolonged 
spasm  of  the  pylorus,  lasting  over  many  hours, 
because  the  acid  in  the  duodenum  takes  so  long 
being  neutralized. 

For  clinical  purposes,  skiagrams  after  a  bismuth 
meal  (one  or  two  ounces  of  bismuth  oxychloride  in 
milk  or  porridge)  are  of  distinguished  value.  The 
patient  should  be  examined  both  standing  and  lying 
down,  and  at  varying  intervals.  Gastroptosis,  gastric 
dilatation,  pyloric  spasm,  and  hour-glass  contraction 
become  quite  evident.  In  the  last  case  the  con- 
nection of  the  two  sacs  is  between  their  upper  portions, 
not  at  the  lowest  point — the  latter  appearance  is  of 
little  significance.  Percussion  and  auscultation  may 
frequently  be  proved  inaccurate  by  skiagraphy. 

MOVEMENTS    OF    THE    INTESTINE. 

We  have  always  known  that  the  small  intestine  is 
continually  in  movement,  the  main  character  of  the 
movement  being  an  onward  sweeping  wave  called 
peristalsis,  carrying  the  bowel  contents  from  the 
stomach  to  the  colon.  Peristalsis  consists  of  a  wave 
of  relaxation  pursued  by  a  wave  of  constriction.  It 
is  controlled  by  a  purely  local  mechanism,  and  will 
go  on  after  all  nerves  have  been  severed,  or  even 
after  taking  the  intestines  right  out  of  the  body. 
After  cutting  the  bowel  across,  the  wave  is  stopped 
at  the  point  of  division.  Fortunately  for  the  practice 
of   end-to-end    anastomosis   of    the   intestines,    any 


OF    THE    ALIMENTARY    CANAL       103 

bowel  contents  which  may  be  pushed  through  the 
junction  will  start  a  fresh  wave  of  peristalsis  on  the 
distal  side  of  the  union.  Though  the  movements  are 
not  dependent  on  nerves,  they  can  be  influenced  by 
the  central  nervous  system,  as  every  one  knows  who 
has  suffered  from  an  attack  of  "  exam-funk  diarrhoea.'* 
The  vagus  stimulates  peristaltic  movements ;  the 
splanchnic  nerves  inhibit  them.  In  the  small  intestine 
peristalsis  is  normally  only  from  stomach  to  colon, 
and  a  bismuth  meal  makes  the  journey  in  about 
four  hours.  There  is  a  sort  of  pendulum  swing- 
swang  of  whole  loops  of  bowel  going  on  at  the  same 
time.  In  the  large  intestine  the  conditions  are  very 
different,  and  have  an  important  bearing  on  certain 
operative  procedures.  The  movements  in  man  may 
be  studied  by  skiagraphy  after  bismuth  meals  or 
bismuth  enemata,  and  by  observations  on  patients 
who  have  suffered  various  forms  of  colostomy, 
ileosigmoidostomy,  and  exclusion  operations.  When 
the  abdomen  is  opened,  intestinal  peristalsis  soon 
comes  to  an  end  on  account  of  the  rapid  loss  of  C02 
from  its  walls.  Saline  solution  saturated  with  C02 
restores  the  movements  to  normal. 

Hertz  has  recently  drawn  attention  to  the  functions 
of  the  ileocaecal  sphincter,  which  guards  the  passage 
through  the  ileocaecal  valve,  and  delays  the  entry 
of  the  contents  of  the  small  intestine  until  time  has 
been  allowed  for  proper  absorption  of  food-stuffs. 
Skiagraphy  after  bismuth  meals  shows  that  the  last 
few  inches  of  the  ileum  remain  full  for  four  or  five 
hours  after  the  stomach  is  empty.  In  cases  of 
chronic    appendicitis    this    sphincter    may    remain 


104    STUDIES   IN   CLINICAL  PHYSIOLOGY 

tightly  contracted  for  as  long  as  twenty-four  hours — 
a  highly  significant  observation,  as  we  shall  see. 
Whenever  food  is  taken  into  the  stomach,  the  ileo- 
cecal sphincter  is  reflexly  inhibited,  and  the  last 
contents  of  the  ileum  pass  through. 

The  rectum  is  of  course  under  direct  control  of 
the  centre  near  the  tip  of  the  spinal  cord,  the  motor 
path  being  the  pelvic  visceral  nerves  from  the  second 
to  the  fifth  sacral  roots ;  the  sympathetic  system 
also  supplies  the  rectum.  The  physiology  of  defeca- 
tion is  well  known,  and  need  not  detain  us. 

In  the  caecum  and  the  ascending,  transverse, 
descending,  and  pelvic  portions  of  the  colon,  however, 
the  motor  functions  are  involuntary,  as  in  the  small 
intestine,  but  with  some  striking  differences.  The 
food  residue  does  not  travel  at  a  slow  regular  rate 
of  progress  through  the  large  intestine.  It  lingers 
in  particular  localities,  such  as  the  caecum  and 
ascending  colon,  the  middle  of  the  transverse  colon, 
the  pelvic  colon,  and  the  rectum,  for  hours  at  a  time, 
and  although  it  has  been  denied,  it  is  certain  that 
antiperistalsis  occurs,  but  not  over  great  lengths  of 
the  bowel.  In  the  small  intestine  antiperistalsis  is 
rare  and  pathological.  Three  or  four  times  a  day, 
and  especially  by  a  gastrocolic  reflex  after  taking 
food,  the  intestinal  contents  are  carried  onwards 
for  several  feet  by  massive  waves  of  peristalsis, 
of  which  the  patient  is  normally  quite  unconscious. 
These  waves  have  been  witnessed  by  a  number  of 
observers.  Here  we  have  the  explanation  of  "  lien- 
teric  "  diarrhoea  immediately  following  a  meal,  and 
also  of  the  pain  after  food  met  with  by  some  sufferers 


OF    THE    ALIMENTARY    CANAL       105 

from  chronic  constipation.  The  bismuth  meal 
normally  reaches  the  pelvic  colon  in  about  twenty- 
four  hours. 

The  existence  of  currents  of  antiperistalsis  is 
very  important  surgically.  Many  patients  on 
whom  ileosigmoidostomy  (turning  the  ileum  into 
the  pelvic  colon  or  sigmoid)  has  been  performed  for 
growth  of  the  ascending  colon  have  suffered  great 
subsequent  discomfort  from  the  passage  of  gas  and 
faeces  into  the  blind  loop  of  colon,  from  the  opening 
into  the  sigmoid  up  into  the  descending  colon,  and 
so  round  towards  the  caecum.  In  some  cases  a 
second  operation  has  been  necessary.  In  all  ana- 
stomoses and  excisions  of  the  large  intestine  this 
physiological  factor  must  be  calculated  upon  and 
provided  for.  In  some  cases  an  appendicostomy  has 
been  performed  to  allow  flatus  to  escape  and  to  make 
lavage  possible. 

Before  turning  from  the  motor  functions  of  the 
intestines,  another  experimental  observation  merits 
attention.  Pawlow  found  that  strong  stimulation  of 
any  sensory  nerves  might  cause,  in  dogs,  prolonged 
reflex  arrest  of  peristalsis.  Injury  of  abdominal 
viscera  was  particularly  likely  to  do  so.  Cannon  and 
Murphy  have  shown  that  even  gentle  manipulation 
of  the  bowel  causes  cessation  of  all  intestinal 
movements  for  three  hours  or  more.  The  condition 
might  be  described  as  "  intestinal  shock."  It  is  of 
great  surgical  importance.  Arrest  of  peristalsis,  quite 
apart  from  peritonitis,  occasionally  follows  strangu- 
lated hernia,  even  after  successful  operation  ;  it  may 
accompany  gall-stone  colic,  and  it  may  even  occur  as 


106    STUDIES   IN   CLINICAL  PHYSIOLOGY 

a  neurosis  or  in  association  with  organic  nervous 
disease.  Some  interesting  cases  are  reported  by 
Walton  in  a  discussion  of  the  subject.  The  milder 
degrees  of  the  condition  will  yield  to  turpentine 
enemata  and  to  saline  purges,  but  there  are  instances 
in  which  all  drugs  are  vomited  and  the  block  seems 
to  be  too  high  for  enemata  to  act.  Here  we  may 
try  the  effect  of  physostigmine  (eserine)  salicylate, 
in  T^irgr.  doses,  given  hypodermically  every  four 
hours  for  six  doses.  This  drug  has  been  used  for 
years  in  Vienna  and  Germany,  though  but  little  in 
England.  Our  personal  experience  of  it  is  favourable. 
Walton  shows  by  a  chart  that  the  evacuations  when 
this  drug  is  given  after  abdominal  operations  are  much 
more  frequent  than  without  it..  It  is  scarcely  at  all 
aperient  in  health,  working  best  when  the  local 
nerve  ganglia  in  the  intestine  are  thrown  out  of 
action.  It  is  of  course  an  old  and  well-known 
remedy,  acting  like  pilocarpine  by  stimulating  the 
nerve  endings  in  unstriped  muscle.  Pituitary  ex- 
tract often  works  well  in  these  cases. 

A  few  further  points  may  be  summarized  briefly. 

Intestinal  colic  is  due  to  some  interference  with  the 
normal  relation  between  the  wave  of  relaxation  and 
the  following  wave  of  contraction,  which  make  up 
normal  peristalsis. 

Ordinary  constipation  is  rarely  due  to  any  prolonga- 
tion of  the  normal  four  hours  taken  by  the  bismuth 
meal  to  pass  from  the  stomach  to  the  caecum.  Some- 
times the  delay  is  in  the  whole  length  of  the  colon  ; 
sometimes  the  faeces  reach  the  rectum  and  pelvic 
colon  in  good  time,  but  are  retained  there.     There 


OF    THE    ALIMENTARY    CANAL       107 

is  a  condition  described  by  Sir  Arbuthnot  Lane,  and 
demonstrated  by  skiagraphy  by  Jordan,  in  which 
the  lower  end  of  the  ileum  is  kinked.  This  is  one 
of  the  causes  of  chronic  intestinal  stasis.  Another 
cause  is  adhesions  round  the  appendix,  which  perhaps 
leads  to  prolonged  contraction  of  the  ileocecal 
sphincter.  In  these  cases  there  is  delay  in  the  small 
intestine. 

The  saline  aperients  do  not  induce  any  hastening 
of  its  contents  through  the  small  intestine,  and  as  they 
may  produce  purgation  in  less  than  four  hours,  it  is 
possible  that  they  are  absorbed  in  the  stomach, 
carried  by  the  blood,  and  re-excreted  in  the  colon 
(Hertz,  Schlesinger,  and  Cook). 

Large  bismuth  enemata  are  able  to  force  the  ileo- 
cecal valve  and  enter  the  small  intestine. 

In  animals,  lateral  union  of  two  coils  of  intestine 
induces  much  more  stasis  than  end-to-end  anasto- 
mosis. 

The  movements  of  the  intestines  are  to  some  extent 
excited  by  a  hormone  produced  after  meals  in  the 
gastric  mucosa,  extracts  of  which,  during  digestion 
but  not  during  starvation,  will  excite  peristalsis 
when  given  by  intravenous  injection.  This  hormone 
is  also  stored  in  the  spleen.  Under  the  name  of 
"  hormonal  "  it  has  been  introduced  into  medicine, 
and  is  of  value  both  for  cases  of  intestinal  paralysis 
after  operation,  and  also  for  chronic  constipation. 
A  single  injection  often  cures  an  old-standing  con- 
stipation. Unfortunately  it  is  not  always  active, 
and  there  have  been  a  few  fatalities,  probably  due 
to  extraneous  products  in  the  splenic  extract. 


108    STUDIES   IN   CLINICAL  PHYSIOLOGY 

SENSATION    IN    THE    ALIMENTARY    CANAL. 

In  his  recent  Goulstonian  Lecture,  Hertz  shows 
that  the  sensory  functions  of  the  viscera  are  much 
more  limited  than  those  of  the  skin.  The  stomach 
and  intestine  do  not  possess  any  temperature  sense 
or  any  tactile  sense,  nor  is  cutting  painful,  but  pulling 
on  the  serous  coat  gives  rise  to  severe  pain.  The 
feeling  of  heat  or  cold  after  swallowing  liquids  is 
appreciated  by  the  lower  end  of  the  oesophagus. 
Temperature  and  tactile  sense  are  quite  well  developed 
in  the  oesophagus,  and  localization  is  very  accurate — 
seldom  more  than  an  inch  out. 

Hydrochloric  acid  may  be  poured  into  the  stomach, 
either  through  a  stomach-tube  or  a  gastrostomy 
wound,  without  producing  any  sensation  at  all, 
even  if  the  percentage  rises  to  0*5  or  even  2,  and  this 
is  true  also  in  cases  of  gastric  ulcer.  Alcohol  does 
excite  a  burning  feeling.  Distention  of  the  stomach 
causes  a  sensation  of  fullness  ;  the  amount  of  dis- 
tension necessary  depends  on  the  tonicity  of  the 
gastric  muscles.  Gastralgia,  whatever  its  cause,  is  due 
to  colicky,  irregular  contractions  of  the  muscle,  the 
pylorus  remaining  closed.  There  is  often  a  referred 
pain  or  tenderness  in  the  cutaneous  area  also.  The 
pain  of  peritonitis  is  probably  quite  a  different  thing. 
Sensation  in  the  intestine  corresponds  closely  in  its 
physiology  to  sensation  in  the  stomach.  The  anal 
canal,  however,  can  detect  thermal  and  tactile  stimuli. 

Carlson  has  recently  shown,  in  a  patient  with  a 
gastric  fistula,  that  the  sensation  which  we  call 
hunger  is  due  to  waves  of  peristalsis  in  the  empty 


OF    THE    ALIMENTARY    CANAL       109 

stomach,  of  which  he  was  able  to  obtain  a  graphic 
record. 

VARIATIONS    IN    THE    HYDROCHLORIC  ACID    OF 
THE    STOMACH. 

The  amount  of  acid  normally  present  as  free  HC1 
is  given  differently  by  different  physiologists,  some 
following  Topfer  and  relying  on  amido-azo-benzol  as 
the  indicator,  others  using  the  more  accurate  but 
somewhat  tedious  method  of  Willcox.* 

It  has  been  customary  to  take  the  normal  quantity 
of  free  HC1  as  0-2  per  cent,  but  Panton  and  Tidy 
and  other  workers  show  that  o-i  is  more  accurate. 
The  total  gastric  acidity  is  about  50  c.c.  of  decinormal 
acid. 

The  contradictory  results  obtained  by  various 
workers  are  worthy  of  explanation.  The  significant 
figure,  the  o-i  per  cent  of  HC1,  means  (a)  HC1  which 
has  already  got  to  work  on  and  combined  with 
protein  in  the  food,  together  with  (b)  any  free  HC1  still 
unattached.  Obviously,  a  larger  or  more  albuminous 
test-meal  would  reduce  the  free  HC1  still  further  in 
any  stomach,  however  normal  the  acidity.  In  spite 
of  this,  some  still  prefer  to  estimate  the  free  HC1  and 
to  regard  it  as  the  significant  figure  ;  they  take  the 
normal  to  be  0*02  per  cent  after  a  test-meal,  the 
remaining  o-o8  having  combined  with  the  food. 

The  total  acidity  of  course  includes  lactic  acid  and 
any  other  fermentation  acids,  also  acid  phosphates, 
and  is  of  no  great  importance. 

*  Lancet,  1905,  i,  p.   1566. 


110    STUDIES   IN   CLINICAL   PHYSIOLOGY 

The  most  reliable  test  for  the  presence  of  HC1  is 
Gunsberg's  (phloroglucin  and  vanillin)  ;  this  is  too 
well  known  to  need  description.  It  is  merely  a 
qualitative  test. 

By  whichever  method  the  estimation  is  made,  it 
would  appear  that  diet  exercises  little  or  no  effect 
on  the  percentage  of  active  hydrochloric  acid, 
although  it  so  markedly  affects  the  pepsin.  Never- 
theless, the  percentage  of  acid  is  liable  to  change, 
and  the  changes  are  of  great  value  for  both  diagnosis 
and  treatment. 

Increased  relative  amount  of  HC1  is  particularly 
common  in  gastric  ulcer,  so  much  so  that  an  analysis 
of  a  test-meal  is  of  diagnostic  importance.  It  is 
also  seen  in  duodenal  ulcer,  and,  as  has  recently  been 
pointed  out,  in  many  other  affections  of  the  alimentary 
canal,  such  as  appendicitis.  It  is  probable  that  the 
cases  which  have  been  diagnosed  as  simple  hyper- 
chlorhydria  have  usually  some  latent  disease,  if  not 
in  the  stomach  or  duodenum,  then  in  the  gall-bladder, 
kidney,  or  appendix,  and  removal  of  the  offending 
organ  will  cure  the  hyperchlorhydria.  The  charac- 
teristic symptom  of  this  condition  is  "  hunger- 
pain,"  that  is,  a  feeling  of  gnawing  of  the  stomach, 
which  may  be  only  a  discomfort  or  may  amount  to 
positive  pain ;  it  occurs  two  or  three  hours  after  a 
meal,  and  is  relieved  by  food  or  alkalies.  It  is  proba- 
bly due  to  the  spasmodic  contraction  of  the  pylorus 
set  up  by  the  long  persistence  of  the  acidity  on  the 
duodenal  side.  Another  view  is  that  it  is  caused 
by  incipient  self-digestion  of  the  stomach.  This  is 
normally  guarded  against  by  an  anti-pepsin  in  the 


OF    THE    ALIMENTARY    CANAL       ill 

mucous  membrane  reversing  the  activity  of  the 
gastric  juice,  but  the  continual  presence  of  an 
abnormally  powerful  combination  of  acid  and  pepsin 
breaks  down  the  resistance,  just  as  is  seen  in  an 
exaggerated  degree  when  a  healthy  man  dies  suddenly 
during  the  process  of  digestion  ;  the  supply  of  anti- 
pepsin  fails  with  the  circulation,  and  a  big  hole  is 
dissolved  through  the  stomach  wall  post  mortem. 
It  is  highly  probable  that  hyperchlorhydria  is  a 
cause  as  well  as  a  consequence  of  gastric  ulcer ; 
certainly  it  determines  the  peculiar  punched-out 
character  which  the  typical  round  ulcer  assumes. 
It  is  significant  that  more  than  one  such  lesion  is 
frequently  present,  as  though  the  excessively  acid 
juice  resulting  from  the  irritation  of  some  initial 
abrasion  not  only  had  deepened  that  lesion  into  an 
ulcer  but  had  determined  the  formation  of  others 
also.  It  is  again  significant  that  the  typical  punched- 
out  ulcer  occurs  just  where  the  acid  has  access,  and 
nowhere  else — at  the  lower  orifice  of  the  oesophagus, 
in  the  stomach,  and  in  the  first  two  inches  of  the 
duodenum,  while  in  the  jejunum  it  is  unknown 
except  at  the  site  of  a  previous  gastrojejunostomy 
opening,  and  not  even  then  unless  this  operation 
has  failed  to  cure  the  hyperchlorhydria,  which  usually 
means  that  the  orifice  was  too  small  or  badly  placed. 
Another  evil  consequence  of  excessive  HC1  is  spasm 
of  the  pylorus,  which  may  lead  to  dilatation  of  the 
stomach.  A  curious  and  suggestive  symptom  is  pyrosis, 
a  periodical  copious  secretion  of  saliva,  probably  de- 
signed to  neutralize  the  acidity  when  swallowed. 
In  infants,  Willcox  and  R.  Miller  have  stated  that 


112    STUDIES   IN   CLINICAL  PHYSIOLOGY 

there  are  two  types  of  dyspepsia  causing  pain, 
wasting,  vomiting,  and  constipation.  One  is  con- 
genital stenosis  of  the  pylorus,  in  which  the  HC1  is 
subnormal  but  the  pepsin  (which  may  be  conveniently 
tested  by  the  curdling  effect  on  milk)  is  excessive  ; 
and  mucin  is  also  in  excess.  The  other  is  "  acid 
dyspepsia,"  in  which  the  HC1  is  excessive  and  the 
ferments  are  subnormal.  In  this  case  peristaltic 
waves  may  be  seen,  but  the  pyloric  tumour  is  not 
felt.  The  prognosis  is  very  much  better  than  in 
congenital  stenosis,  and  operation  is  not  needed  as 
it  so  often  is  in  the  more  serious  condition. 

Enough  has  been  said  to  show  that  hyperchlor- 
hydria  and  its  advertisement,  "  hunger-pain,"  are 
more  than  an  inconvenience  to  the  patient ;  they 
are  in  many  cases  the  consequence  and  in  other  cases 
the  precursor  of  serious  organic  mischief  which  may 
lead  to  dilated  stomach,  to  chronic  gastric  ulcer — 
which  in  its  turn  is  very  apt  to  become  malignant — 
or  to  an  abdominal  catastrophe  from  perforation  of 
the  stomach  or  duodenum. 

When  the.  hyperchlorhydria  is  not  associated  with, 
or  precedes,  ulceration  of  the  stomach  or  duodenum, 
the  appendix  or  gall-bladder  is  probably  at  fault. 
The  appendix,  for  instance,  may  show  adhesions  or 
stenosis. 

Sherren  found  the  appendix  normal  in  only  4  out 
of  65  cases  of  duodenal  ulcer,  and  5  out  of  41  cases 
of  gastric  ulcer.  Moynihan,  Paterson,  the  Mayos  and 
others  have  shown  that  the  majority  of  the  gastric 
and  duodenal  ulcers  met  with  on  the  operation  table 
are  associated  with  appendicitis.     The  sequence  is. 


OF    THE    ALIMENTARY    CANAL       113 

first  appendicitis,  then  hyperchlorhydria,  and  thirdly 
ulceration. 

Chronic  dyspepsia  is  often  the  only  complaint  in 
persons  who  have  no  hyperchlorhydria,  show  no 
local  symptoms  of  trouble  in  the  appendix,  but  are 
cured  by  removal  of  that  organ.  The  majority  of 
patients  diagnosed  as  gastric  ulcer  in  the  medical 
wards  of  a  hospital,  and  recovering  without  operation, 
in  all  probability  have  no  ulcer  at 'all,  but  only  reflex 
gastric  symptoms  following  on  gall-stones,  movable 
kidney,  or  appendicitis.  In  20  per  cent  of  patients 
with  symptoms  of  gastric  ulcer  operated  on  at  the 
Bristol  Royal  Infirmary,  no  ulcer  was  found.  Why 
disease  of  the  appendix,  or  gall-bladder,  should  cause 
these  symptoms  it  is  difficult  to  decide.  It  can 
scarcely  be  due  to  toxic  absorption,  as  the  appendix 
may  be  quite  fibrotic.  Perhaps  the  simplest  explana- 
tion is  that  the  ileocaecal  sphincter  remains  tightly 
closed  and  produces  back-pressure.  In  other  cases 
there  may  be  irregular  gastric  peristalsis  and  hyper- 
chlorhydria as  a  nervous  reflex. 

The  treatment  of  hyperchlorhydria  is  as  follows. 
Medical  means  will  often  give  a  large  measure  of 
relief.  Taking  food,  and  especially  a  hard-boiled 
e^g,  when  the  pain  comes  on  will  generally  abate  the 
symptoms.  Alkalies  are  indicated,  especially  mag- 
nesia, which  has  two  advantages  :  it  does  not  dis- 
solve and  exert  all  its  effect  in  a  few  minutes,  and  it 
does  not  give  off  carbon  dioxide  as  the  carbonates  do. 
The  bismuth  lozenges  of  the  B.P.  are  convenient 
to  carry  and  very  successful  in  stopping  the  dis- 
comfort.    We    will     barely    mention     such    useful 

8 


114    STUDIES   IN   CLINICAL  PHYSIOLOGY 

measures  as  rest  in  bed,  milk  diet,  and  lavage.  Pawlow 
on  theoretical  grounds  recommends  fats  and  oils  to 
check  the  flow  of  the  gastric  juice.  These  measures 
are  of  course  not  applicable  in  the  presence  of  an  acute 
ulcer  causing  haemorrhage. 

If  these  means  are  not  successful,  it  is  very  desirable 
to  perform  laparotomy  and  to  explore  the  stomach, 
duodenum,  appendix,  kidney,  and  gall-bladder.  If 
gastric  or  duodenal  ulcer  is  present,  gastrojejunostomy 
is  of  course  indicated.  If  no  abnormality  can  be 
discovered  in  either  stomach  or  duodenum  without 
opening  into  them  (which  is  seldom  if  ever  called 
for),  it  may  be  that  some  adhesions  or  kinking  of  the 
appendix  may  be  found,  and  removal  of  the  organ 
will  effect  a  cure  in  many  of  the  cases  but  not  all. 
It  is  shown  by  Paterson,  the  Mayos,  Sherren,  and 
others  that  about  75  per  cent  of  the  many  hundreds 
of  cases  of  dyspepsia  without  ulceration  treated  by 
removal  of  the  appendix  are  cured.  It  might  be 
well  to  do  a  gastrojejunostomy  at  the  same  time  ; 
one  of  Paterson's  failures  was  subsequently  relieved 
by  this  means.  This  operation  may  lead  to  a 
permanent  cure  of  pain,  vomiting,  or  hsematemesis, 
even  when  no  abnormality  can  be  found.*  The 
important  point  is  that  it  is  not  right  to  do  the 
short-circuiting    operation    on    a    normal    stomach 


*  This  statement  has  been  denied  by  one  or  two  reviewers  of  the 
first  edition,  but  is  nevertheless  persisted  in.  Admittedly  the 
results  are  not  so  good  as  when  a  definite  ulcer  is  found,  but  out  of 
ten  cases  treated  by  gastrojejunostomy  in  which  nothing  was 
discovered,  six  were  much  improved  years  afterwards.  See  A. 
Rendle  Short,  "  End-results  of  Operations  on  the  Stomach  and 
Duodenum,"  Bristol  Med.-Chir.  Jour.,  1911,  p.  220. 


OF    THE    ALIMENTARY    CANAL       115 

without  also  exploring  the  appendix  and  gall- 
bladder. Soltau  Fenwick  states  that  of  112  cases 
of  hyperchlorhydria,  in  34  the  stomach  and  duodenum 
were  normal ;  in  22  of  these  the  appendix  was 
at  fault,  and  in  12  gall-stones  were  present.  In 
9  cases  appendix  trouble  complicated  gastric  or  duo- 
denal ulcer.  In  66  patients  an  ulcer  was  present  in  the 
stomach  or  duodenum  ;  4  of  these  were  malignant. 

It  is  a  remarkable  fact  that  severe  and  repeated 
haemorrhage  from  the  stomach  may  take  place  in  the 
absence  of  any  ulcer.  Out  of  seven  cases  recently 
operated  on  for  haematemesis  at  the  Bristol  Royal 
Infirmary,  in  only  two  was  an  ulcer  found.  A  con- 
dition of  universal  weeping  of  blood,  called  "  gastro- 
staxis,"  occurs  in  these  cases,  and  with  the 
gastroscope  the  mucous  membrane  may  be  seen  to 
ooze  blood  wherever  it  is  touched. 

Hydrochloric  Acid  Deficient. — It  is  well  known  that 
the  HC1  in  the  gastric  juice  is  deficient  or  absent  in 
cases  of  cancer  of  the  stomach,  but  the  practical 
value  of  this  is  lessened  by  the  fact  that  old-standing 
gastritis,  or  cancer  of  other  organs  than  the  stomach, 
may  abolish  the  HC1.  On  the  other  hand,  cancer 
more  often  than  not  is  preceded  by  ulcer,  and  there 
will  be  a  stage  in  which  the  hyperchlorhydria  has 
not  yet  passed  off  although  cancer  is  already  present. 
Nevertheless,  we  cannot  afford  to  neglect  the  chemical 
test  in  the  diagnosis  of  eancer  of  the  stomach,  as  the 
other  early  signs  are  often  equally  dubious. 

In  persons  beyond  middle  age,  absent  hydro- 
chloric acid  is  not  uncommon  without  any  apparent 
cause  or  consequence. 


116    STUDIES   IN   CLINICAL  PHYSIOLOGY 

THE    PHYSIOLOGY    OF    GASTROJEJUNOSTOMY. 

What  effect  is  produced  upon  the  functions  of  the 
alimentary  canal  by  the  operation  of  gastrojejuno- 
stomy ?  We  have  to  ask  :  (i)  Does  the  food  pass 
through  the  new  opening  or  by  the  pylorus  ?  (2) 
What  is  the  effect  upon  the  gastric  juice  ?  and  (3) 
What  is  the  effect  upon  the  absorption  of  proteins, 
fats,  and  carbohydrates  ? 

Some  light  has  been  thrown  upon  the  first  of  these 
questions  by  watching  with  the  %-rays  the  course 
taken  by  a  meal  containing  bismuth  oxide,  and  it 
would  appear,  as  might  have  been  expected,  that 
both  routes  are  followed,  unless  either  the  pylorus 
or  the  artificial  opening  is  or  becomes  greatly  nar- 
rowed. On  this  subject  the  writings  of  Cannon 
and  Gray  may  be  consulted. 

The  former  used  cats  with  a  normal  stomach  on 
which  the  operation  had  been  performed,  and  natur- 
ally the  tendency  was  for  the  meal  to  take  the  pyloric 
route. 

Hartel*  has  made  a  study  by  this  means  of  22 
patients  operated  on  months  or  years  before.  About 
half  of  them,  including  those  in  which  pyloric  stenosis 
was  found  at  the  operation  to  be  severe,  emptied  only 
by  the  new  opening ;  in  the  others  the  food  took 
both  directions.  In  one  case  it  appeared  to  pass  out 
only  by  the  pylorus. 

The  effect  upon  the  gastric  juice  is  nil  if  it  has 
previously  been  normal ;  if  hyperchlorhydria  was 
present,     an     efficient     gastrojejunostomy     appears 

*  Deut.  Zeit.  Chirurg.,  1911. 


OP    THE    ALIMENTARY    CANAL       117 

invariably  to  restore  the  amount  of  acid  to  normal. 
Stenosis  of  the  opening  may  be  followed  by  a  return 
to  the  greater  acidity.  If  the  HC1  is  absent,  however, 
the  operation  will  seldom,  if  ever,  cause  it  to  appear. 

That  there  cannot  be  any  serious  loss  of  power  to 
digest  and  absorb  food-stuffs  is  shown  by  the  remark- 
able way  in  which  the  great  majority  of  cases  operated 
on  become  fat  and  flourishing  after  gastrojejunostomy 
for  non-malignant  affections,  the  improved  condition 
being  maintained  for  many  years.  There  is  at  least 
one  patient  who  at  the  age  of  seven  was  described 
by  his  father  as  strong  and  healthy,  with  good  appe- 
tite and  exceedingly  good  digestion,  after  a  gastro- 
jejunostomy at  the  age  of  eight  weeks  for  pyloric 
stenosis.  Paterson  has  proved  that  the  amount  of 
fat  and  protein  passed  in  the  faeces  without  assimila- 
tion is  very  little  greater  than  in  the  normal  individual. 
In  four  cases  it  was  only  about  2  per  cent  above 
normal ;  that  is,  the  faeces  contained  about  9  to 
9-5  per  cent  of  protein  nitrogen  taken  as  food 
instead  of  the  normal  77  per  cent.  Much  less 
favourable  results  previously  published  by  Joslin 
were  due  to  the  fact  that  he  used  cancerous  cases  on 
which  to  experiment.  Paterson' s  results  are  confirmed 
by  Cameron,*  who  finds  that  the  only  ill-effect  is  some 
slight  diminution  in  the  power  of  absorbing  fat. 

The  relief  afforded  by  a  gastrojejunostomy  in 
conditions  where  there  is  no  organic  obstruction 
depends  on  two  main  factors  :  it  drains  away  the 
acid  juice,  so  that  no  excess  can  accumulate,  and 

*  Brit.  Med.  Jour.,  1908,  i,  p.  140. 


118    STUDIES   IN   CLINICAL  PHYSIOLOGY 

when  pain  is  being  caused  by  strong  gastric  peristalsis 
against  a  spasmodically  closed  pylorus  it  provides  a 
safety-valve.  The  beneficial  effect  on  ulcers  and 
hsematemesis  is  probably  due  to  the  withdrawal  of 
the  acid  and  the  prevention  of  distention. 

Feeding  after  Gastrostomy. — Pawlow's  experi- 
ments, above  referred  to,  give  a  valuable  hint  as 
to  the  feeding  of  patients  who  are  unable  to  swallow 
and  have  suffered  a  gastrostomy.  It  is  well  known 
that  they  may  fail  to  make  progress  even  when  the 
operation  has  apparently  not  been  postponed  too  long. 
Sometimes  they  will  request  that  they  should  still 
be  allowed  to  take  food  into  the  mouth  "  just  to 
taste  it."  Evidently  they  lack  the  first  secretion  of 
gastric  juice  due  to  the  relish  with  which  the  food  is 
tasted  and  swallowed,  and  digestion  may  in  conse- 
quence be  very  imperfect.  This  may  be  overcome 
by  the  simple  device  of  adding  some  form  of  extrac- 
tives to  the  feed,  such  as  beef-tea,  gravy,  soup,  or  a 
meat  essence.  Thus  the  chemical  mechanism  is 
brought  into  play  though  the  nervous  reflex  fails. 
Excellent  practical  results  have  been  obtained  by 
this  expedient. 

THE    SECRETION    OF    PANCREATIC    JUICE. 

This  was  first  thought  by  Pawlow  to  be  due  to  a 
reflex  through  the  vagus,  but  it  has  been  shown  by 
Bayliss  and  Starling  that  the  stimulus  is  in  reality 
chemical,  though  it  is  not  impossible  that  a  secretion 
can  also  be  induced  by  the  vagus.  When  the  hydro- 
chloric acid  of  the  gastric  juice  touches  the  mucous 


OF    THE    ALIMENTARY    CANAL       119 

membrane  of  the  duodenum,  a  soluble  chemical 
substance  is  formed  called  "  secretin,"  which  passes 
into  the  rootlets  of  the  portal  vein,  is  carried  to  the 
liver  and  heart,  and  thence  all  over  the  body.  Some 
of  it  in  due  course  reaches  the  pancreas,  and  a  flow  of 
pancreatic  juice  is  at  once  instituted  and  continues 
as  long  as  the  acid  contents  of  the  stomach  continue 
to  enter  the  duodenum.  The  secretion  acts  chemi- 
cally on  the  pancreatic  cells,  liberating  steapsin  from 
pro-steapsin,  amylopsin  from  pro-amylopsin,  and 
trypsinogen  from  pro-trypsinogen.  There  is  some 
evidence  that  secretin  stimulates  also  the  activity  of 
the  liver  cells,  thus  pouring  into  the  bowel  not  only 
pancreatic  juice  but  bile. 

We  find  in  this  mechanism  a  clear  indication  for 
the  administration  of  hydrochloric  acid  in  cases 
where  that  of  the  gastric  juice  is  deficient.  At  least 
we  may  be  able  to  preserve  for  the  patient  the 
activity  of  his  pancreatic  juice,  which  is  likely  to  be 
suppressed  when  the  usual  stimulus  is  lacking.  The 
exhibition  of  secretin  itself  has  so  far  been  a  failure  ; 
it  is  not  absorbed  from  the  bowel,  and  giving  it 
subcutaneously  produces  dangerous  depression,  due 
apparently  to  other  substances,  which  we  do  not 
know  how  to  separate,  extracted  along  with  it  from 
the  duodenal  mucous  membrane. 

Pawlow  and  his  followers  have  described  a  mar- 
vellous adaptation  of  the  various  pancreatic  ferments 
to  the  work  in  hand  ;  thus,  they  thought  that  a 
meat  diet  called  forth  much  trypsin,  and  a  starchy 
diet  much  amylopsin.  These  statements  were  made 
before  we  knew  that  the  flow  of  pancreatic  juice 


120    STUDIES   IN   CLINICAL  PHYSIOLOGY 

was  started  by  secretin,  which  in  its  turn  depends 
on  the  amount  of  HC1  coming  through  from  the 
stomach.  A  still  more  disturbing  factor  is  the  action 
of  the  ferment  in  the  intestinal  juice  called  entero- 
kinase,  without  which  trypsin  is  inert,  being  secreted 
in  an  inactive  form  called  trypsinogen  and  only 
activated  by  the  enterokinase.  More  recent  work, 
taking  these  new  facts  into  account,  shows  that  the 
composition  of  the  pancreatic  juice  does  not  vary. 
It  is  probable,  however,  that  other  substances  besides 
hydrochloric  acid  have  the  power  of  calling  forth 
pancreatic  juice,  and,  indeed,  if  it  were  not  so, 
patients  with  cancer  of  the  stomach  would  usually 
starve.  Workers  in  Pawlow's  laboratory  have 
demonstrated  that  the  most  important  of  these  are 
fat  and  soaps,  and  the  action  is  similar  to  that  of 
the  gastric  juice,  namely,  by  exciting  the  formation 
of  a  secretin.  It  is  very  probable,  also,  that  the 
sight  and  smell  of  food  set  up  a  flow  of  pancreatic 
juice,  but  it  is  difficult  to  be  sure  of  this. 

Pawlow's  operative  experience  in  making  pancreatic 
fistulae  in  dogs  and  in  the  after-treatment  may 
suggest  devices  for  surgical  practice.  To  obtain  a 
permanent  fistula  it  was  necessary  to  bring  the  duct 
out  on  the  abdominal  wall,  and  still  to  preserve  its 
natural  orifice,  otherwise  it  closed  rapidly.  Therefore 
a  small  square  of  duodenum  containing  the  opening 
of  the  duct  was  transplanted  to  the  skin.  With 
careful  nursing  and  treatment,  such  dogs  would  live 
for  months  or  years. 

There  were  two  principal  points  in  the  after-treat- 
ment.    At  first  there  was  great  difficulty  on  account 


OF    THE    ALIMENTARY    CANAL       121 

of  tryptic  digestion  of  the  skin  around  the  wound, 
such  as  is  so  trying  for  surgeon  and  patient  in  some 
cases  after  operation  for  acute  pancreatitis,  pancreatic 
cysts,  rupture  of  the  pancreas,  or  artificial  anus  in 
the  small  intestine.  One  of  Pawlow's  dogs,  suffering 
in  this  way,  kept  on  tearing  down  mortar  from  the 
wall  to  lie  upon,  and  by  so  doing  greatly  improved 
the  condition.  The  hint  was  acted  upon,  and  after- 
wards a  bed  of  sand  or  mortar  was  always  provided, 
and  the  excoriation  avoided. 

About  a  month  after  the  operation,  most  of  the 
animals  became  very  weak  and  refused  food,  and 
several  died.  Yet  there  had  been  no  loss  of  weight, 
there  was  no  peritonitis,  and  merely  ligating  the 
pancreatic  duct  produced  no  such  symptoms ; 
indeed,  no  special  harm  resulted.  Pawlow  concluded 
that  the  loss  of  juice  must  be  the  cause  of  the  trouble, 
so  a  diet  of  milk  and  bread,  which  excites  the  smallest 
flow  of  secretion,  was  substituted  for  meat,  which 
excites  the  greatest  flow,  and  alkalies  were  given 
regularly  by  mouth.  By  these  means  the  dangerous 
symptoms  were  entirely  averted. 

Both  the  above  experiences  may  help  us  in 
dealing  with  some  special  difficulties  in  surgical  cases 
after  operations  on  the  pancreas.  For  the  sand  or 
mortar,  bags  containing  some  drying  powder  would 
probably  be  substituted. 

THE    BILE. 

We  may  dismiss  the  recent  researches  on  the  bile 
in  a  very  few  words,  as  their  clinical  bearing  is  not 
yet  apparent. 


122    STUDIES   IN  CLINICAL  PHYSIOLOGY 

The  secretion  of  bile  by  the  liver  cells  is  excited  by 
secretin,  just  as  is  the  pancreatic  secretion.  No  bile, 
however,  enters  the  duodenum  except  when  food  is 
there,  two  hours  after  a  meal.  The  quantities  of  bile 
and  pancreatic  juice  poured  into  the  intestine  rise 
and  fall  exactly  together.  The  reflex  contractions 
of  the  gall-bladder  which  determine  this  flow  of  bile 
are  brought  about  by  the  presence  of  fat  or  of  extrac- 
tives in  the  duodenum.  Here  probably  we  find  the 
explanation  of  any  virtue  which  olive  oil  may  have  in 
getting  rid  of  gall-stones,  because  it  is  highly  question- 
able whether  any  of  the  oil  is  actually  excreted  by 
the  bile,  or  in  any  other  way  brought  into  contact 
with  the  concretions  so  as  to  dissolve  them. 

Of  the  many  functions  which  have  been  charged 
upon  the  bile,  the  most  important  is  that  of  an 
intensifier  of  the  action  of  the  pancreatic  juice. 
The  pancreatic  ferments  have  their  activity  enhanced 
threefold  in  the  presence  of  the  sodium  taurocholate 
and  glycocholate  of  the  bile.  Moreover,  these  salts 
dissolve  fatty  acids,  and  so  help  in  the  absorption 
of  fats. 

ABSORPTION     OF    PROTEINS. 

There  remains  to  be  described  a  fundamental 
change  in  our  views  of  the  digestion  and  absorption 
of  proteins.  It  was  formerly  taught  that  the  gastric 
and  pancreatic  ferments  converted  the  albumin  of 
the  food  into  soluble,  diffusible  bodies  called  peptones  ; 
that  these  passed  through  the  intestinal  wall  into  the 
blood-stream,  and  in  so  doing  were  by  some  means 
built  up  again  into  the  proteins  of  the  blood.     Some 


OF    THE    ALIMENTARY    CANAL       123 

readers  may  recollect  a  Cleavage  Theory,  suggesting 
that  half  of  these  peptones  were  further  acted  on  by 
the  trypsin  of  the  pancreatic  juice  and  broken  down 
into  two  aminoacids  called  leucin  and  tyrosin,  whose 
fate  was  in  doubt.  The  modern  view  is  very  different. 
The  researches  of  Fischer,  Kossel,  and  others  have 
thrown  a  flood  of  light  on  the  composition  of  the 
protein  molecule.  We  now  know  that  protein  con- 
sists of  a  complicated  chain  of  the  bodies  called 
aminoacids  (that  is,  organic  acids  of  which  a  hydrogen 
has  been  replaced  by  the  NH2  group).  These  may 
be  classified  as  monoamines  (as  leucin,  glycin), 
diamines  (as  arginin,  lysin),  and  aromatic  amines 
(as  tyrosin,  tryptophan).  By  the  trypsin  of  the 
pancreatic  juice  proteins  are  resolved  into  their 
various  components,  and  consequently  a  mixture,  in 
differing  proportions,  of  these  aminoacids  is  found 
in  the  intestine.  Some  peptone  appears  to  resist 
further  disintegration  by  the  pancreatic  ferment, 
but  there  is  a  ferment  in  both  the  pancreatic  and 
intestinal  juices  called  erepsin,  which  completes  the 
action  of  the  gastric  and  pancreatic  juices  by  con- 
verting all  the  peptones  into  aminoacids. 

Neither  albumin  nor  peptone  can  be  absorbed  by 
the  intestine.  They  must  first  be  converted  into 
aminoacids.  These  are  the  actual  substances  which 
traverse  the  intestinal  wall  and  enter  the  blood- 
stream. They  do  not  circulate  as  serum  albumin, 
but  as  aminoacids,  and  are  taken  up  by  the  tissue 
proteins  according  to  their  needs.  Should  these 
require  more  of  the  aromatic  amines,  they  will 
abstract  tyrosin  or  tryptophan  from  the  blood,  and 


124    STUDIES   IN   CLINICAL  PHYSIOLOGY 

so  on.  Any  aminoacids  that  are  in  excess  of  the 
requirements  of  the  body  are  broken  down  by  the 
liver  to  urea,  and  excreted  by  the  kidney.  This 
constitutes  the  so-called  exogenous  origin  of  urea. 

The  evidence  for  these  fundamental  changes  in 
our  view  of  the  absorption  of  proteins  may  be 
summarized  briefly  as  follows : — We  now  know  that 

(a).  Aminoacids  are  abundantly  formed  in  the 
intestine. 

(b).  Feeding  on  aminoacids  obtained  by  tryptic 
digestion,  though  not  by  sulphuric  acid  disintegra- 
tion of  protein,  will  sustain  life.  Gelatin  will  not 
sustain  life,  because  it  lacks  the  aromatic  amines, 
but  if  it  is  given  with  tyrosin  and  tryptophan,  the 
animal  lives. 

(c).  During  protein  absorption,  it  is  not  the  pro- 
teins (serum  albumin  and  globulin)  which  increase  in 
the  blood,  but  the  nitrogenous  constituents  of  the 
plasma  which  are  not  coagulated  by  heat. 

(d).  Van  Slyke  has  demonstrated  a  marked  rise 
in  the  quantity  of  aminoacids  in  the  blood  during 
protein  digestion,  although  it  seems  to  last  only  a 
very  short  time.  These  acids  disappear  from  the 
circulating  blood  within  a  few  minutes  of  injection. 

Carlyle  said  that  an  error  is  never  proved  to  be  an 
error  until  it  is  shown  how  the  error  arose,  and  this 
is  possible  in  regard  to  the  older  theory,  that  peptones 
were  converted  by  the  intestinal  epithelium  into 
albumin.  The  disappearance  of  the  peptone  in 
contact  with  the  intestinal  wall  was  taken  to  indicate 
a  conversion  into  albumin,  because  the  nature  and 
function  of  the  ferment  erepsin  were  not  then  known. 


OF    THE    ALIMENTARY     CANAL       125 

The  erepsin  had  converted  the  peptone  into  amino- 
acids. 

We  must  not  hope  therefore  when  we  feed  a 
patient  on  peptonized  foods,  that  we  have  completely 
saved  him  the  necessity  of  digesting  them.  We  have 
carried  the  process  only  part  of  the  way.  It  is  not 
feasible,  perhaps,  to  feed  him  on  aminoacids,  because 
the  prolonged  pancreatic  digestion  makes  the  food 
unpleasantly  bitter  and  might  cause  diarrhoea ; 
aminoacids  are  not  normal  occupants  of  the  stomach. 

Absorption  in  the  Colon. — We  may  sum  up  the 
ordinary  functions  of  the  various  parts  of  the  bowel 
with  regard  to  absorption  thus  : — 

Drugs,  salts,  and  sugars  are  absorbed  in  the 
stomach. 

Proteins  (as  aminoacids),  carbohydrates  (as  sugar), 
and  fats  (as  soap  and  glycerin)  are  absorbed  in  the 
small  intestine. 

Water  is  absorbed  in  the  large  intestine. 

The  practical  physician  or  surgeon  is  concerned 
with  the  physiologist's  answer  to  two  questions. 
First,  Is  the  colon  a  necessary  organ,  or  may  it  be 
eliminated  with  safety  ?  Second,  Can  the  large 
intestine  absorb  useful  foodstuffs  in  case  of  need  ? 

With  regard  to  the  first  point,  we  are  at  once  con- 
fronted with  the  fact  that  in  some  bats  the  colon  is 
exceedingly  short.  Again,  it  is  well  known  that 
patients  with  an  artificial  anus  in  the  caecum  are  able 
to  keep  up  their  nutrition.  The  same  is  true  after 
the  ileum  has  been  cut  across  and  turned  into  the 
sigmoid.     Careful    analyses    made    by    Groves    and 


126    STUDIES   IN    CLINICAL  PHYSIOLOGY 

Walker  Hall  under  these  conditions  show  that  the 
normal  amount  of  water  can  still  be  absorbed  by  the 
short  piece  of  rectum  and  sigmoid  traversed  by  the 
food  ;  the  faeces  are  not  too  fluid.  By  comparing  the 
amount  of  water  in  the  intestinal  contents  at  the 
ileocaecal  valve  and  as  passed  naturally  in  man, 
they  conclude  that  the  colon  absorbs  about  10  to 
20  per  cent  of  water  from  the  fseces.  Bacteria 
make  up  nearly  half  the  .weight  of  the  faeces  as 
passed  normally.  Treves,  Lane,  and  others  have 
excised  almost  the  whole  colon  without  the  patient's 
nutrition  suffering. 

We  conclude  then  that  the  colon  is  not  a  necessary 
organ.  If,  however,  a  permanent  artificial  anus  is 
made  in  the  ileum  more  than  12  to  18  inches  away 
from  the  ileocaecal  valve,  absorption  is  inadequate, 
and  the  patient  dies  of  starvation. 

Turning  to  the  second  question,  it  is  scarcely 
necessary  to  call  attention  to  its  very  great 
importance.  If  the  colon  cannot  absorb  a  reasonable 
quantity  of  foodstuffs,  the  whole  theory  of  feeding 
by  nutrient  enemata  would  collapse. 

In  the  experiments  described  above,  Groves  and 
Walker  Hall  found  that  the  absorption  of  nitrogen 
and  fat  by  the  colon  was  so  small  as  to  be  negligible. 
Laidlaw  and  Ryffel,  analysing  the  urine  during  rectal 
feeding,  found  that  the  nitrogen  output  corresponded 
pretty  closely  to  the  published  figures  for  pro- 
fessional fasting  men  at  the  same  date  of  starvation  ; 
the  enemata  used  were,  however,  not  particularly 
suitable,  consisting  of  the  whites  of  nine  eggs,  six 
ounces  of  raw  starch,   and  twenty-four  ounces  of 


OF    THE    ALIMENTARY    CANAL       127 

peptonized  milk.  The  albumin  and  starch  were 
probably  not  touched.  Langdon  Brown  found  no 
difference  in  the  urea  of  the  urine,  whether  the 
patients  were  given  peptonized  milk  or  normal  saline. 
Careful  analysis  of  the  figures  given  by  Boyd  and 
Robertson,  and  also  a  number  of  observations  made 
by  the  present  writer,  furnish  convincing  evidence 
that,  as  measured  by  the  standard  of  the  nitrogen 
output  in  the  urine,  the  absorption  of  nitrogenous 
foodstuffs  from  the  rectum  is  practically  nil. 

Sharkey  and  others  claim  that  a  good  deal  of 
nitrogen  can  be  absorbed  by  the  rectum,  basing  their 
findings  on  the  analysis  of  rectal  washings  ;  but  this 
method  is  open  to  criticism,  as  sometimes,  in  spite  of 
washing  out,  the  patient  may  pass  an  enormous 
putrid  evacuation,  showing  that  lavage  was  not 
effectual. 

Now  this  failure  to  absorb  might  be  due  to  one 
of  two  causes.  First,  it  may  be  that  the  large 
intestine  has  no  power  of  absorbing  nitrogenous 
foodstuffs  in  any  form.  Second,  it  may  be  that  no 
erepsin  is  present  in  its  secretion,  so  that  no  amino- 
acids  are  formed  from  the  peptone  of  the  enema. 
The  crucial  experiment  is,  Can  aminoacids  be 
absorbed  ? 

To  determine  this  the  writer,  with  Dr.  Bywaters, 
has  made  daily  analyses  of  nitrogen  in  the  urine  by 
the  Kjeldahl  method  in  patients  to  whom  enemata 
were  given,  either  of  milk  pancreatized  for  twenty- 
four  hours,  so  as  to  convert  most  of  the  protein  into 
aminoacids,  or  in  other  cases  of  synthetic  amino- 
acids   (Merck).     Usually    ordinary   ward    nutrients, 


128    STUDIES   IN   CLINICAL  PHYSIOLOGY 

peptonized  for  twenty  minutes,  were  given  for  a 
few  days  first,  and  then  the  aminoacid  preparations 
used  instead.  In  each  of  five  patients  the  nitrogen 
output  in  the  urine  was  greatly  increased  by  the 
use  of  aminoacids  in  the  nutrients.  Figures  of  two 
such  cases  are  given  in  the  Appendix. 

We  conclude,  therefore,  that  aminoacids  can  be 
absorbed,  and  that  we  may  hope  to  give  nourishment 
to  patients  by  rectal  injections  of  milk  pancreatized 
for  twenty-four  hours,  although  ordinary  peptonized 
milk  is  a  failure. 

It  is  quite  certain  that  dextrose  can  be  absorbed 
from  the  rectum,  because  it  will  cure  acidosis  when 
given  in  this  way,  and  also  it  will  raise  the  respiratory 
quotient  by  increasing  the  amount  of  C02  expired. 
Boyd  and  Robertson  showed  that  practically  no 
sugar  can  be  recovered  from  the  rectal  washings  of 
a  patient  given  peptone  and  sugar  enemata,  although 
peptone  is  always  returned.  Lactose  appears  not 
to  be  absorbed  ;   it  fails  to  control  acidosis. 

It  is  very  difficult  to  obtain  evidence  as  to  whether 
fats  are  absorbed.  In  a  patient  who  had  a  fistula 
of  the  thoracic  duct,  only  from  3*7  to  5*5  per  cent 
of  the  fat  given  per  rectum  was  recovered  from  the 
fistula. 

In  another  patient  the  thoracic  duct  was  blocked 
and  a  lymphatic  vessel  had  ruptured  into  the  urinary 
passages,  so  that  most  of  the  fat  absorbed  by  the 
lacteals  escaped  into  the  urine,  which  became  milky 
after  a  fatty  meal  (chyluria).  There  was  no  chyluria 
when  all  fats  were  stopped  by  mouth  and  nutrient 
enemata  containing  milk  administered. 


OF    THE    ALIMENTARY    CANAL       129 

It  must  not  be  supposed  that  rectal  feeding 
supplies  absolute  rest  to  the  stomach.  It  may  be 
observed  in  patients  with  a  gastrostomy  wound  that 
each  nutrient  enema  excites  a  reflex  flow  of  gastric 
juice. 

Those  who  believe  in  the  possibility  of  feeding 
patients  satisfactorily  by  nutrient  enemata  usually 
rely  upon  some  incorrect  published  analyses  by 
Ewald,  an  observation  by  Leube  that  a  dog  can  be 
kept  alive  for  many  months  by  injections  of  chopped 
meat  and  pancreas  (this  method  causes  toxic  sym- 
ptoms in  man),  and  the  remarkable  fact  that  the 
weight  may  be  fairly  well  sustained  at  first.  This 
happens  even  if  nothing  but  water  is  given,  and  is 
due  to  the  fact  that  the  patients,  usually  sufferers 
from  haematemesis,  are  exsanguinated  to  start  with 
and  greedily  absorb  water.  Patients  have  been 
kept  alive  on  nutrients  for  several  weeks,  but  it 
is  well  known  that  there  are  sometimes  sudden  and 
unaccountable  deaths.  It  must  not  be  forgotten 
that  if  water  is  supplied  life  will  usually  be  prolonged 
for  a  month  with  no  food  at  all,  and  in  one  instance 
a  man  was  alive  after  sixty-four  days  of  complete 
starvation.  If  water  also  is  withheld,  death  takes 
place  in  about  a  week  ;  but  a  girl  buried  in  an  Italian 
earthquake  lived  eleven  days  without  either  food 
or  drink. 

We  conclude,  therefore,  that  feeding  with  nutrients 
composed  of  peptonized  milk  is  sheer  starvation, 
but  that  better  results  may  be  obtained  with 
enemata  composed  of  dextrose  and  long-pancreatized 
milk. 


130  THE    ALIMENTARY    CANAL 

REFERENCES. 

Pawlow. — "  The  Work  of  the  Digestive  Glands."  Trans- 
lated by  W.  H.  Thompson.  2nd  Edition.  Griffin  &  Co., 
1910. 

Starling. — "  Recent  Advances  in  the  Physiology  of  Diges- 
tion." London,  1906.  (Gives  an  excellent  list  of 
authorities.) 

Langdon  Brown. — "  Physiological  Principles  in  Treatment." 
2nd  Edition.     London,  191  o. 

Hertz. — "  The  Sensibility  of  the  Alimentary  Canal."  Oxford 
Med.  Public,  191 1. 

Soltau  Fenwick. — Proc.  Royal  Soc.  Med.,  Surgical  Section, 
1910,  p.  177. 

Paterson. — Ibid.,  p.  187. 

Cannon. — "  The  Mechanical  Factors  of  Digestion."  Arnold 
&  Co.,  1911. 

Willcox. — Lancet,  1905,  i,  p.  1566  ;    1908,  ii,  p.  220. 

Walton. — Ibid.,  1908,  ii,  pp.  17,  85. 

Groves. — Proc.  Royal.  Soc.  Med.,  vol.  ii,  1909,  part  iii. 
Surgical  Section,  p.  121. 

Langdon  Brown. — Proc.  Royal  Soc.  Med.,  Therapeutics 
Section,  191 1,  p.  63. 

Hertz. — Jour,  of  Physiol.,  1913,  vol.  xlvii,  pp.  54,  57. 

Sherren. — Brit.  Jour,  of  Surg.,  1914,  Jan.,  p.  390. 

Rendle  Short  and  Bywaters. — Brit.  Med.  Jour.,  1913,  i, 
p.  1361. 

Carlson. — Amer.  Jour.  Physiol.,  1913,  p.  8. 


131 


CHAPTER    VIII. 
THE     HEMORRHAGIC    DIATHESIS. 

The  physiology  of  the  coagulation  of  the  blood — Fibrinolysis — 
Haemophilia — Pathology  of  haemophilia — Treatment  of  haemo- 
philia— The  therapeutics  of  calcium  salts. 

WE  are  still  far  from  a  clear  conception  of  the 
exact  pathology  of  haemophilia,  purpura,  and 
the  hemorrhagic  tendency  in  jaundice,  but  it  will 
be  only  by  a  sound  understanding  of  the  normal 
processes  of  coagulation  of  the  blood  that  we  shall 
be  able  to  comprehend  the  abnormal. 

The  phenomena  of  blood-clotting  are  beautifully 
designed  to  avoid  two  opposing  evils  ;  if  no  provision 
was  made  for  fibrin  formation  every  injury  would  be 
fatal ;  but  on  the  other  hand,  if  all  the  essentials  for 
the  process  were  already  present  in  the  plasma,  the 
circulation  would  immediately  be  brought  to  a 
standstill  by  intravascular  thrombosis.  Therefore 
coagulation  is  made  to  be  dependent  on  contact  with 
damaged  cells,  either  tissue-cells  or  leucocytes,  and 
in  particular  with  the  nucleoprotein  constituting 
their  nuclei,  while  the  intact  lining  endothelium  of 
the  blood-vessels  has  the  power  of  preventing  clotting. 
We  have  all  been  told  that  a  length  of  jugular  vein 
containing  blood  may  be  tied  at  each  end  and  hung 
up  for  a  week,  and  no  clotting  occurs  until  damaged 
tissue-cells  are  added.     Thus  we  find  that  the  very 


132     THE    HEMORRHAGIC    DIATHESIS 

incision  or  laceration  which  excites  the  haemorrhage 
provides  also  the  wherewithal  to  stop  it.  The 
nucleoprotein  furnished  in  this  way  by  the  tissues  is 
called  thrombokinase. 

Next,  we  know  that  calcium  salts  are  needful  for 
clotting,  and  if  they  are  withdrawn  by  oxalates  or 
citrates,  no  fibrin  will  be  formed.  An  excess  of 
calcium  salts,  however,  delays  clotting. 

Concerning  thrombogen  or  prothrombin  we  cannot 
speak  so  confidently.  It  is  intimately  associated 
with,  and  hard  to  separate  from,  fibrinogen,  but  is 
probably  derived  eventually  from  the  leucocytes 
and  platelets.  Hydrocele  fluid,  which  does  not 
contain  any  corpuscles,  will  not  clot  until  blood  or 
fibrin  is  added. 

The  actual  mother  substance  of  the  fibrin  is  of 
course  the  fibrinogen,  a  protein  in  the  plasma.  There 
is  really  a  double  reaction,  thus  : — 

(i)  Prothrombin       +     Thrombokinase     -f     Calcium  salts 
(  =  thrombogen)        (from  damaged  (in  plasma) 

(?  from  leucocytes)     .leucocytes  or 
tissue-cells) 


Thrombin  (  =  fibrin  ferment) 
(ii)       Thrombin  +  Fibrinogen  (in  plasma) 


Fibrin 


According  to  Mellanby,  the  name  fibrin  ferment 
is  a  misnomer,  as  a  particular  weight  of  thrombin 
will  liberate  only  a  certain  definite  quantity  of  fibrin 
from  fibrinogen,  whereas  a  ferment  knows  no  limits 
to  its  activities. 


THE    HEMORRHAGIC    DIATHESIS      133 

We  have  yet  one  more  provision  to  refer  to.  The 
cells  lining  the  blood-vessels,  and  the  leucocytes 
themselves,  are  not  immortal.  When  they  die, 
thrombokinase  is  shed  out,  and  so  thrombin  would 
be  formed  and  induce  local  clotting.  This  does 
actually  occur  in  phlebitis  and  other  forms  of 
venous  or  arterial  thrombosis.  In  the  physiological 
state,  however,  the  liver  secretes  into  the  blood  an 
antithrombin  sufficient  in  amount  to  deal  with  small 
formations  of  thrombin,  but  not  sufficient  to  interfere 
with  the  natural  process  of  arrest  of  haemorrhage. 

Considerable  variations  take  place  in  the  readiness 
with  which  the  blood  coagulates,  and  it  is  often  easier 
to  understand  why  than  how  this  is  brought  about. 
For  instance,  at  the  end  of  pregnancy  clotting  is 
rapid  ;  in  the  diseases  mentioned  above  it  is  deficient 
or  slow.  After  a  haemorrhage,  the  fibrinoplastic 
(clot-forming)  power  rises  quickly.  Information  may 
be  obtained  by  means  of  the  coagulimeter,  a  standard 
capillary  tube  into  which  the  blood  is  sucked  up  so 
that  the  time  which  it  takes  solidifying  may  be 
measured.  It  requires  some  care  in  practice  to  avoid 
variations  in  the  calibre,  variations  in  temperature, 
the  inclusion  of  lymph  or  clots,  etc. 

Associated  with  deficient  coagulability  there  is 
often  a  tendency  to  effusions  of  plasma  through  the 
capillary  walls  on  account  of  the  low  viscosity  of  the 
blood.  The  symptoms  of  such  a  tendency  to  effusion 
are  liability  to  chilblains,  headaches,  nettlerash  or 
patchy  oedema,  and  transient  or  functional  albu- 
minuria. 

The  conversion  of  fibrinogen  into  fibrin  is  only  the 


134     THE    HEMORRHAGIC    DIATHESIS 

first  stage  of  a  more  prolonged  process,  just  as  the 
very  similar  conversion  of  caseinogen  in  milk  into 
solid  casein  is  only  one  step  in  the  process  of  breaking 
it  down  to  simpler  substances  such  as  peptones  and 
aminoacids. 

The  fibrin  is  not  a  permanent  body.  Even  in 
blood-clot  kept  at  about  400  C,  it  undergoes  partial 
resolution  into  simpler  and  soluble  substances,  under 
the  influence  of  ferments  already  present  in  the  clot, 
called  fibrinolysins.  It  is  probable  that  these,  as 
well  as  leucocytes,  play  -an  important  part  in  deter- 
mining the  resolution  of  fibrin  collections  in  the 
human  body,  such  as  may  be  found  not  only  in 
bruises  and  thromboses  but  also  in  the  lymph-clot 
which  is  the  precursor  of  adhesions  in  the  pleural 
and  peritoneal  cavities.  It  is  well  known  that  these 
adhesions  may  disappear  spontaneously  to  a  remark- 
able degree.  Any  value  which  thiosinamine  and  its 
derivative  fibrolysin  may  have,  given  hypodermically 
to  absorb  young  fibrous  tissue,  may  possibly  be  due 
to  the  production  of  ferments  such  as  these. 

HEMOPHILIA. 
Of  all  the  many  conditions  in  which  the  haemor- 
rhagic  diathesis  is  present,  haemophilia  is  at  once  the 
most  interesting,  the  best  understood,  and  the  most 
tragically  dangerous.  We  will  not  stay  to  speak  of 
the  curious  problems  of  its  inheritance,  nor  of  the 
well-known  tendency  to  bruising,  joint  effusions,  and 
bleeding  after  the  most  trivial  injuries.  One  or  two 
of  its  peculiarities,  however,  deserve  a  word  of 
mention,  as  they  may  throw  a  light  on  the  production 


THE    HEMORRHAGIC    DIATHESIS     135 

of  the  hemorrhagic  tendency.  For  instance,  the 
locality  and  the  nature  of  the  injury  have  some 
significance.  In  a  few  cases,  wounds  below  the  neck 
may  not  bleed  to  excess,  whereas  abrasions  of  the 
most  trifling  description  affecting  the  lips,  cheeks, 
or  gums  may  baffle  all  attempts  to  stanch  the  flow. 
Again,  needle  pricks,  if  small,  do  not  bleed,  probably 
because  the  elastic  skin  seals  over  the  opening  ;  it 
is  even  safe  to  withdraw  blood  from  a  vein.  Further, 
it  is  not  true  that  the  haemorrhage  never  stops.  It 
may  cease  with  or  without  treatment,  sometimes 
permanently,  sometimes  only  to  come  on  again  later. 
If  a  subcutaneous  hematoma  develops,  the  wall  is 
lined  by  well-formed  clot,  but  the  central  portion 
contains  blood  which  shows  no  tendency  to  coagu- 
lation in  spite  of  the  contact  with  clot.  It  is  the 
capillaries,  rather  than  the  arteries,  which  continue 
to  ooze. 

It  will  be  a  matter  of  opinion  whether  under  the 
generic  name  of  haemophilia  we  should  include  cases 
that  arise  every  now  and  then,  in  either  sex,  of  a 
congenital  and  persistent  tendency  to  bruise  and 
bleed  from  every  slight  abrasion,  apart  from  any 
family  history  of  a  similar  kind.  There  is  no  doubt 
that  the  symptoms  and  course  of  some  of  these  cases 
are  identical  with  ordinary  haemophilia,*  and  they 
are  nearly  as  common.  Bulloch  states  that  the 
characteristic  joint  affections  never  occur  except  in 
the  hereditary  class. 


*  See   instances   given   by   Squire,   Brit.    Med.  Jour.,   1910,   i, 
p.  1 1 68  ;   and  Osier,  Lancet,  1910,  i,  p.  1226. 


136     THE    HEMORRHAGIC    DIATHESIS 

PATHOLOGY    OF    H/EMOPHILIA. 

Up  to  a  certain  point  modern  observers  are  agreed 
as  to  the  cause  of  haemophilia.  Ever  since  Sir 
Almroth  Wright,  nearly  twenty  years  ago,  showed 
that  the  coagulation  time  in  these  patients  is  very 
greatly  delayed,  all  students  of  the  disease  who  have 
carefully  fulfilled  the  proper  conditions  have  been 
able  to  establish  his  discovery.  Normal  blood  in  a 
Wright's  coagulimeter  tube  clots  in  five  to  ten  minutes; 
haemophiliac  blood  may  take  anything  from  fifteen 
to  ninety  minutes  to  solidify,  although  the  eventual 
yield  of  fibrin  is  copious  and  firm.  Addis  has  shown 
that  the  coagulation  time  is  exactly  related  to  the 
severity  of  the  tendency  to  bleed,  the  mildest  cases 
yielding  the  shortest  times,  and  the  severe  cases  the 
longest.  It  is  true  that  a  few  who  have  used  the  blood 
shed  out  during  an  actual  haemorrhage  have  found 
no  delay  in  the  coagulation  time,  but  apart  from 
other  fallacies,  such  as  the  danger  of  including  fibrin 
ferment,  the  mere  fact  of  the  continued  bleeding 
makes  the  blood  clot  more  rapidly  both  in  bleeders  and 
in  ordinary  people,  as  Wright  and  Addis  have  shown. 

Another  abnormality  in  the  blood  is  a  frequent 
deficiency  in  polymorphonuclear  leucocytes. 

We  may  take  it  that  the  rival  theory,  that  of  the 
undue  fragility  of  the  vessel  walls,  is  now  definitely 
abandoned.  Morawitz  and  Lossen  have  both  shown 
that  the  oedema  obtained  by  dry-cupping  is  no 
greater  in  haemophiliacs  than  it  is  in  normal 
individuals. 

So  far,  then,  there  is  substantial  agreement. 
When  we  seek  to  go  further,  and  to  inquire  just  which 


THE    HEMORRHAGIC    DIATHESIS     137 

we  are  to  blame  of  the  various  elements  that  take 
part  in  regulating  the  coagulation  of  the  blood,  the 
problem  becomes  complicated. 

Theoretically,  the  delay  might  be  due  to : — 
(i)  Deficient  quantity  or  quality  of  the  fibrinogen  ; 
(2)  Deficiency  or  excess  of  calcium  salts  ;  (3)  De- 
ficient quantity  or  quality  of  the  thrombokinase  ; 

(4)  Deficient  quantity  or  quality  of  the  prothrombin  ; 

(5)  Excess  of  antithrombin. 

In  the  examination  of  these  factors  we  follow  the 
researches  of  Addis.  The  main  point  to  determine 
is  whether  the  delay  is  in  the  first  or  the  second  of 
the  two  reactions  involved, — that  is,  in  the  conversion 
of  prothrombin  into  thrombin,  or  in  the  conversion 
of  fibrinogen  into  fibrin.  It  proves  that  the  former 
is  at  fault ;  the  latter  is  quite  normal.  Haemophiliac 
fibrinogen  is  as  readily  clotted  by  normal  or  by 
haemophiliac  thrombin  as  is  normal  fibrinogen,  and 
normal  fibrinogen  is  easily  clotted  by  thrombin  from 
a  bleeder.  But  the  haemophiliac  blood  must  stand 
a  long  time  before  any  prothrombin  is  converted  into 
thrombin. 

Taking  up  the  points,  then,  in  order  : — 

1.  The  defect  is  not  in  the  fibrinogen,  because  it 
is  readily  clotted  if  isolated  and  treated  with  throm- 
bin. Moreover,  when  clot  does  at  last  form  during 
a  haemorrhage,  it  is  as  firm  and  abundant  as  in 
ordinary  blood. 

2.  The  defect  is  not  in  the  calcium  salts,  because 
analysis  shows  no  abnormality  in  quantity,  and  the 
addition  of  these  salts  to  drawn  haemophiliac  blood, 
though  it  may  hasten  the  time  of  clotting,  does  not 
bring  it  to  normal. 


138     THE    HEMORRHAGIC    DIATHESIS 

3.  The  defect  is  not  in  the  thrombokinase.  Here 
Sahli  joins  issue  with  Addis,  because  the  addition  of 
washed  leucocytes  to  haemophiliac  blood  rapidly 
causes  it  to  clot.  These  may,  however,  bring  in 
prothrombin  as  well  as  thrombokinase,  and  Addis 
shows  that  solutions  of  thrombokinase,  derived  by 
crushing  up  testis  in  saline,  have  far  less  effect  on 
haemophiliac  than  on  normal  blood  unless  very  concen- 
trated extracts  are  used.  Again,  there  is  just  as  much 
thrombokinase  in  the  serum  of  a  bleeder,  squeezed 
out  after  coagulation,  as  in  that  of  a  normal  person. 

4.  It  is  in  the  prothrombin  that  the  defect  lies.  A 
very  little  normal  plasma,  or  a  few  washed  corpuscles 
from  a  normal  person,  restore  the  coagulation  power 
forthwith. 

Addis  believes  that  he  has  directly  proved  the 
point  by  the  adoption  of  the  following  method  for 
isolating  the  prothrombin,  and  at  the  same  time  he 
has  established  that  in  the  hasmorrhagic  diathesis  it  is 
deficient  not  in  quantity  but  only  in  character.  He 
prepared  a  solution  of  fibrinogen  from  normal  or 
haemophiliac  plasma  in  the  ordinary  way  by  precipi- 
tating it  by  passing  a  stream  of  carbon  dioxide  through 
plasma  kept  from  clotting  by  citrate  or  oxalate. 
Fibrinogen  so  obtained,  as  Mellanby  shows,  always 
carries  with  it  prothrombin,  and  in  the  presence  of 
calcium  salts  and  thrombokinase  would  liberate 
thrombin.  Addis,  however,  added  instead  a  trace  of 
thrombin,  which  clotted  the  fibrinogen  and  left  its 
prothrombin  in  solution.  When  a  trace  of  prothrombin 
so  obtained  from  a  normal  blood  was  added  to  haemo- 
philiac blood,  this  promptly  coagulated.    (The  criticism 


THE    HEMORRHAGIC    DIATHESIS     139 

would  of  course  be  that  there  was  some  unused 
thrombin  present  as  well,  too  much  having  been  added 
to  the  fibrinogen.) 

Thus,  the  exact  pathology  of  haemophilia  would  be, 
in  Addis' s  opinion,  a  congenital  defect  in  the  con- 
stitution of  the  prothrombin,  whereby  it  yields 
thrombin  much  too  slowly.  Possibly  the  leucocytes 
are  ultimately  at  fault. 

The  practical  deduction  we  shall  see  later. 

5.  There,  is  no  excess  of  antithrombin  in  the  plasma 
of  the  bleeder.  If  there  were,  the  addition  of  a  trace 
of  normal  blood  would  not  cause  haemophiliac  blood 
to  clot  as  it  does,  because  any  thrombin  in  the  former 
would  be  overpowered  and  destroyed  by  the  anti- 
thrombin in  the  latter. 

To  sum  up,  the  secret  of  haemophilia  lies  in  a 
defective  quality  of  the  prothrombin,  such  that  it 
takes  much  longer  than  usual  to  develop  into 
thrombin.  No  evidence  is  yet  to  hand  to  show 
whether  the  haemorrhagic  tendencies  in  scurvy, 
purpura,  pernicious  anaemia,  and  occasionally  in 
jaundice  have  the  same  explanation. 

It  is  important  to  bear  in  mind  the  fact  that 
certain  cases  of  jaundice  may  ooze  to  death  by 
capillary  haemorrhage  after  operation  ;  most  of  us 
can  recollect  instances  of  this  calamity.  It  has  been 
recommended  to  give  drachm  doses  of  calcium 
chloride  for  three  days  before  the  operation,  but 
probably  a  more  useful  proceeding  would  be  to  take 
the  coagulation  time  by  means  of  a  Wright's  tube, 
and  to  refuse  to  operate  on  any  cases  showing  serious 
delay. 


140     THE    HEMORRHAGIC    DIATHESIS 

TREATMENT    OF 
THE     HEMORRHAGIC    DIATHESIS. 

It  will  be  gathered  that  unfortunately  the  under- 
lying causes  of  haemophilia  do  not  lend  themselves 
to  direct  remedy.  We  cannot,  except  by  one  drastic 
proceeding,  influence  the  quality  or  quantity  of  the 
more  complicated  and  specialized  nbrinoplastic 
elements  in  the  blood,  and  we  can  use  only  those 
means  which  in  a  general  way  are  understood  to 
increase  the  coagulability. 

Sometimes  the  ordinary  surgical  means  such  as 
rest,  pressure,  plugging,  or  adrenalin  may  be  success- 
ful. It  is  usually  advised  not  to  stitch  wounds, 
for  fear  of  bleeding  from  the  punctures,  but  if  these 
are  made  with  a  small,  round-bodied  needle,  the 
elasticity  of  the  skin  will  prevent  oozing.  Therefore, 
if  tight  stitching  would  obviously  bring  useful 
pressure  to  bear,  it  should  be  resorted  to,  but  only 
in  the  skin,  not  in  mucous  membranes. 

It  has  been  advised,  and  the  advice  is  physio- 
logically sound,  to  apply  normal  human  blood  to  the 
oozing  point.  Unhappily,  even  if  a  mass  of  clot  is 
formed  over  the  wound,  it  soon  gets  pushed  away  by 
the  collection  of  unclotted  blood  beneath  it.  For 
the  normal  arrest  of  haemorrhage  it  is  necessary  either 
that  clotting  should  take  place  inside  the  bleeding 
vessel  or  that  it  should  fill  the  wound  so  tightly  about 
this  vessel  as  to  present  a  complete  block  to  the  flow. 
It  is  often  impossible  to  get  the  remedy  near  enough 
to  the  actual  rent  in  the  artery  or  capillary  to  bring 
this  about,  and  the  shape  of  the  wound  may  not  lend 
itself  to  filling  up  tightly  with  firm  clot.    Nevertheless, 


THE    HEMORRHAGIC    DIATHESIS     141 

the  method  is  simple  and  painless,  and  has  some- 
times succeeded. 

Styptics  such  as  ferric  chloride,  tannin,  or  alum 
may  be  applied  to  the  wound,  but  they  are  painful 
and  lead  to  much  sloughing,  so  it  is  well  first  to 
give  a  brief  trial  to  fresh  normal  blood  applied  by 
wool  pledgets,  and  to  Wright's  physiological  styptic 
(thrombokinase) ,  composed  of  one  part  of  minced 
thymus  in  ten  parts  of  normal  saline.  This  produces 
a  firm  clot,  but  does  not  act  as  quickly  as  the 
escharotic  styptics. 

Internally,  Wright  gives  calcium  salts,  preferably 
the  lactate,  but  admittedly  this  is  a  bow  drawn  at  a 
venture,  because  the  calcium  is  often  absorbed  very 
badly,  and  may  already  be  at  the  optimum  in  the 
blood.  The  first  difficulty  may  be  obviated  in  some 
patients  by  using  magnesium  lactate  or  carbonate. 
The  doses  of  any  of  these  drugs  should  be  60  grains 
for  adults,  and  15  grains  for  children,  at  once,  followed 
by  10-grain  doses  three  times  a  day  for  three  days 
for  adults,  with  a  corresponding  reduction  for 
children.  Calcium  salts  reverse  their  effect  after 
three  days. 

To  the  same  authority  we  are  indebted  for  the 
suggestion  that  we  should  administer  carbon  dioxide 
gas,  either  from  a  Kipp's  apparatus  containing 
marble  and  hydrochloric  acid,  or  from  a  cylinder  of 
the  gas.  Venous  blood  is  much  more  coagulable 
than  arterial.     Dyspnoea  should  be  avoided. 

Weil  recommends  the  injection  of  horse-serum,, 
conveniently  obtained  as  diphtheria  antitoxin.  It 
probably  increases  the  rate  of    blood-clotting,   but 


142     THE    HEMORRHAGIC    DIATHESIS 

apparently  not  until  many  hours  have  passed,  and 
consequently  it  often  fails  in  practice. 

There  remains  one  last  resort  in  the  most  desperate 
cases,  and  no  patient  should  be  allowed  to  die  of 
haemophilia  without  its  being  attempted.  We  have 
seen  that  there  is  only  one  way  to  restore  prompt 
coagulability  to  haemophiliac  blood,  and  that  is  to 
supply  normal  blood. 

Goodman  has  published  a  well-written,  almost 
dramatic  description  of  his  treatment  of  a  Jewish 
boy,  aged  two  and  a  half,  a  well-known  bleeder  and 
member  of  a  bleeder  family,  who  was  moribund  from 
haemorrhage  from  a  cut  inside  the  cheek,  which  had 
oozed  incessantly  for  two  days.  Pressure,  adrenalin, 
styptics,  calcium  salts,  and  horse-serum  (antitoxin) 
had  all  been  tried  in  vain,  and  finally  the  child  lay 
motionless  and  pallid,  scarcely  breathing,  with 
haemoglobin  down  to  12  per  cent,  and  haemorrhage 
continuing. 

Goodman  decided  to  inject  normal  human  blood. 
A  donor,  not  a  relative,  was  tested  by  Wassermann's 
test  for  syphilis,  and  declared  free.  Under  novocain 
anaesthesia  his  radial  artery  was  connected  by  an 
Elsberg  cannula  with  the  child's  femoral  vein. 
There  were  some  initial  difficulties  in  getting  a  good 
flow,  and  hot  cloths  had  to  be  applied  ;  finally  the 
basilic  vein  was  substituted  for  the  femoral  on  account 
of  differences  in  the  level  of  these  patients.  Trans- 
fusion was  continued  for  twenty-eight  minutes. 
During  this  time  colour  gradually  mounted  up  in 
the  cheeks  of  the  little  sufferer,  the  breathing  became 
audible  once  more,  the  almost  watery  blood  acquired 


THE    HEMORRHAGIC     DIATHESIS      143 

t 
its  normal  hue,  and  the  haemoglobin  rose  to  70  per 

cent.      Most    significant    of    all,    the    bleeding    was 

completely  and  permanently  arrested,  and  there  was 

no  haemorrhage  from  the  incisions.     Both  made  an 

excellent  recovery.     The  donor  required  to  rest  in 

bed  for  a  few  days. 

The  above-described  case  by  no  means  stands 
alone  ;  excellent  results  have  been  obtained  in 
septicaemia  and  in  coal-gas  poisoning  as  well  as  in 
haemophilia.  It  will  not  do  to  use  animal's  blood, 
because  bloods  of  different  species  are  mutually 
destructive. 

The  connection  between  the  two  patients  may  be 
made  by  dissecting  out  a  short  length  of  artery  and 
vein  respectively  under  local  anaesthesia,  and  uniting 
them  either  by  a  short  oiled  glass  tube  or  by  Carrel's 
immediate  suture.  Of  course  great  care  must  be 
taken  not  to  inject  clots  or  air,  and  the  technical 
difficulties  may  be  considerable. 

When  a  healthy  adult  supplies  blood  to  an  infant, 
the  donor  suffers  no  ill-effects,  except  that  rest  for 
a  few  days  is  desirable.  In  many  cases,  however, 
especially  if  older  children  or  adults  are  to  be  trans- 
fused, it  would  be  well  to  provide  two  donors,  either 
simultaneously  or  successively.  But  probably  it  is 
not  necessary  to  transfuse  large  quantities.  We  have 
seen  that  quite  a  trifling  addition  of  normal  blood 
will  make  it  possible  for  haemophiliac  blood  to  clot 
promptly,  and  there  is  no  need  in  most  cases  to  do 
more  than  stanch  the  bleeding.  Rest,  fresh  air, 
plenty  of  fluids,  and  iron,  will  speed  the  convalescence. 


144     THE    HEMORRHAGIC    DIATHESIS 

THE    THERAPEUTICS     OF    CALCIUM    SALTS. 

So  much  interest  has  lately  attached  to  this  subject 
that  brief  mention  only  will  be  called  for  of  the  uses 
to  which  calcium  salts  have  been  put.  It  has  long 
been  recognized  by  physiologists  that  they  are 
essential  to  the  continued  success  of  perfusion  fluids, 
and  now  we  know  that  they  control  the  coagulation 
and  viscosity  of  the  blood,  and  probably  the  functions 
of  the  ovary  and  parathyroid  glands  also. 

Remarkable  results  have  been  obtained  in  many 
cases  by  giving  calcium  lactate  in  15-gr.  doses  thrice  a 
day,  for  three  days  only,  in  the  following  conditions : 

Transient  or  functional  albuminuria. 

"  Lymphatic "  headache  frequently  recurring  in 
anaemic  young  women. 

Some  urticarial  eruptions. 

Chilblains.  In  this  common  complaint  it  may 
work  like  a  charm. 

All  varieties  of  tetany. 

The  symptoms  of  the  menopause  are  sometimes 
greatly  relieved  by  calcium  lactate. 

In  all  the  above,  however,  there  is  one  constantly 
recurring  source  of  fallacy.  The  power  to  absorb 
calcium  from  the  bowel  varies  much  in  different 
people,  and  some  observers  record  negative  results 
after  giving  the  drug.  Magnesium  salts  will  some- 
times be  more  effectual  if  calcium  fails  to  get  into 

the  blood. 

REFERENCES. 
Mellanby. — Jour,  of  Physiology,  1909,  p.  28. 
Sir  Almroth  Wright. — Allbutt's  System  of  Medicine,  1909, 

vol.  v,  p.  918. 
Addis. — Quart.  Jour,  of  Medicine,  Oct.,  1910,  p.  14  ;    British 

Medical  Jour.,  1910  (ii),  p.  1422. 
Goodman. — Annals  of  Surg.,  Oct.,  1910,  p.  457. 


145 


CHAPTER    IX. 

THE    PHYSIOLOGY   OF    URIC   ACID   AND 
OTHER    URINARY    DEPOSITS. 

Uric   Acid :     Derivation   from   foodstuffs ;     Derivation    from    the 
tissues  ;    The   purin  bodies  ;   Calcium   oxalate — Cystin 

THE  substances  which  may  form  a  crystalline 
deposit  in  the  urine  are  many,  but  we  shall 
here  refer  only  to  three,  namely,  uric  acid  and  the 
urates,   oxalate   of  calcium,   and   cystin. 

URIC    ACID    AND    THE    URATES. 

For  many  years  totally  erroneous  views  were  held 
by  physiologists  with  regard  to  the  origin  of  these 
substances.  It  has  been  customary  to  argue  the 
physiology  of  the  mammal  from  that  of  the  bird, 
with  disastrous  results.  Removal,  or  rather  isola- 
tion, of  the  liver  in  geese  was  shown  by  Minkowski 
to  diminish  the  output  of  uric  acid,  whilst  ammonium 
salts  and  lactic  acid  were  increased  in  the  urine. 
Hence  it  was  concluded  that  uric  acid  was  formed 
in  the  liver  from  ammonium  salts  and  lactic  acid  ; 
and  for  birds  and  reptiles  this  is  true.  In  mammals, 
the  metabolism  is  totally  different.  The  end  product 
of  protein  metabolism  in  birds  and  snakes  is  uric 
acid ;  in  mammals  it  is  urea.  It  by  no  means 
follows,  therefore,  that  uric  acid  is  formed  in  the 

10 


146     THE    PHYSIOLOGY   OF    URIC   ACID 

mammalian  liver.  We  may  say  at  once  that  urea 
is  formed  in  the  mammalian  liver. 

We  now  believe  that  uric  acid  in  mammals  is 
derived  partly  from  certain  substances  in  the  food,  and 
partly  from  the  breaking  down  of  cell  nuclei,  which 
takes  place  in  most  organs  in  the  body,  notably  in  the 
spleen.  From  these  organs  it  is  carried  to  the  kidney, 
and  excreted  thereby.  As  we  shall  see,  however, 
there  is  a  curious  complicating  factor,  in  that  any 
uric  acid  which  chances  to  reach  the  liver  instead 
of  the  kidney  is  changed  into  urea.  The  liver, 
like  all  other  glands,  furnishes  a  little  uric  acid 
to  the  blood,  but  it  probably  destroys  more  than 
it  supplies. 

The  researches  of  Fischer  and  his  pupils  have 
demonstrated  that  uric  acid  belongs  to  a  group  of 
bodies  containing  a  hypothetical  nucleus,  the  purin 
ring.  Other  members  of  the  group  are  xanthin 
and  hypoxanthin,  which  occur  in  muscle  and  meat 
extracts ;  caffeine,  which  occurs  in  coffee ;  and 
theobromine,  in  cocoa.  Many  foodstuffs  contain 
small  quantities  of  these  bodies  ;  amongst  vegetables, 
peas,  beans,  lentils,  and  asparagus  may  be  mentioned 
as  yielding  them  ;  there  is  also  a  small  quantity  in 
beer.  Milk,  eggs,  and  most  vegetables  contain 
practically  no  purin  bodies. 

The  nuclei  of  all  cells  in  the  animal  body  contain 
a  special  form  of  protein  called  nucleoprotein,  in 
which  the  protein  is  combined  with  nucleic  acid 
On  ultimate  analysis  this  substance  yields,  amongst 
other  products,  certain  purin  bodies,  called  guanin 
and  adenin. 


AND    OTHER    URINARY    DEPOSITS      147 

The  uric  acid  and  other  purin  bodies  in  the  urine 
(xanthin,  etc.)  are  derived  from  two  sources,  referred 
to  as  exogenous  and  endogenous.  By  exogenous 
origin  we  mean  that  substances  capable  of  yielding 
purin  bodies  taken  as  food  are  broken  down  by  the 
digestive  juices,  the  purin  bodies  are  then  liberated 
and  absorbed  by  the  blood,  carried,  with  or  without 
alteration,  to  the  kidneys,  and  by  them  excreted  in 
the  urine.  These  have  never  been  built  up  into  the 
protoplasm  of  the  living  cells  of  the  body.  By 
endogenous  origin  we  mean  that  purin  bodies  are 
end  products  of  the  breaking  down  of  certain  of  the 
constituents  of  the  living  protoplasm  of  the  indi- 
vidual. In  other  words,  the  purin  bodies  of  the  urine 
may  be  derived  from  the  food,  or  from  the  living 
tissues  of  the  body.  The  normal  man  on  an  ordinary 
diet  excretes  exogenous  and  endogenous  purin  in 
about  equal  quantities. 

Variations  in  the  amount  of  uric  acid  excreted 
may  be  Effected,  then,  by  variations  in  the  food,  or 
by  variations  in  the  breaking  down  of  the  tissues. 

Considering  first  the  effect  of  diet,  it  is  found  that 
on  a  purin-free  diet  the  uric  acid  and  the  purin  bodies 
in  the  urine  drop  to  about  half  the  ordinary  amount. 
Feeding  on  meat,  broths,  coffee,  etc.,  increases  the 
excretion  of  the  uric  acid  and  other  purin  bodies,  and 
the  same  effect  may  be  obtained  by  feeding  with 
hypoxanthin  itself.  Again,  any  tissue  rich  in  nucleo- 
protein,  that  is  to  say  rich  in  cell-nuclei,  will,  if  given 
by  the  mouth,  increase  the  output  of  uric  acid  and 
purin  bodies.  Calf's  thymus,  the  roe  of  fishes,  liver, 
and  pancreas  (sweetbread)  all  have  this  effect.     To 


148     THE    PHYSIOLOGY   OF    URIC   ACID 

sum  up,  uric  acid  and  other  purin  bodies  are'derived 
from  feeding  on  : — 

1.  Purin  bodies  in  meat,  broths,  coffee,  etc. 

2.  Nucleoproteins. 

Strange  to  say,  feeding  on  uric  acid  itself  causes  no 
increased  output  in  the  urine  ;  instead,  there  is  a 
greater  excretion  of  urea.  If  urates  are  injected  into 
the  blood-stream,  uric  acid  and  urea  are  both  in- 
creased in  the  urine,  only  part  of  the  uric  acid  injected 
being  recovered  as  such.  Evidently  then  some  organ 
is  capable  of  converting  uric  acid  into  urea.  This 
organ  is  the  liver,  and  a  uricolytic  ferment,  destroying 
uric  acid,  may  be  obtained  from  it. 

The  whole  of  the  purin  body  given  by  the  mouth 
does  not  appear  as  purin  body  in  the  urine.  A  good 
deal  appears  as  urea.  There  is  a  fraction,  constant 
for  the  species,  representing  to  what  extent  this  takes 
place.  In  man,  half  the  purin  body  absorbed  is 
destroyed  by  the  liver.  In  the  dog,  nineteen- 
twentieths  are  destroyed.  The  difference  appears  to 
depend  on  the  differences  in  relative  size  of  the 
blood-vessels  of  the  liver  and  kidney  in  the  various 
species,  those  of  the  dog's  liver  being  very  large. 

It  has  yet  to  be  explained  how  it  is  that  adenin 
and  guanin — derived  from  nucleoprotein — and  xan- 
thin  and  hypoxanthin — derived  from  muscle — come 
to  be  excreted  partly  as  urea,  partly  as  uric  acid,  and 
partly  as  less  oxidized  purin  bodies. 

It  is  now  known  that  many  organs  of  the  body, 
notably  the  spleen,  contain  a  remarkable  series  of 
ferments  acting  upon  these  substances.  Thus  there 
have  been  obtained  : — 


AND    OTHER    URINARY    DEPOSITS      149 

Nuclease,  splitting  nucleoprotein,  and  liberating 
guanin  and  adenin. 

Guanase,  converting  guanin  (C6HgN40*NH2)  into 
xanthin  (C5H4N40.2). 

Adenase,  converting  adenin  (C5H3N4"NH.2)  into 
hypoxanthin  (C5H4N40). 

Oxidase,  converting  xanthin  (C5H4N402)  and  hypo- 
xanthin (C5H4N40)  into  uric  acid  (C5H4N403). 

If  spleen  pulp,  which  is  rich  in  nuclei,  is  left  to 
digest  itself  at  a  suitable  temperature,  xanthin  and 
uric  acid  are  formed  in  situ. 

The  purin  bodies,  then,  split  off  from  nucleoprotein 
in  the  body  or  derived  from  food  containing  purin 
bodies  or  nucleoprotein,  are  acted  on  in  the  spleen 
and  in  all  other  organs  by  these  ferments,  and  even- 
tually uric  acid  would  be  produced.  This  is  excreted 
by  the  kidney  as  rapidly  as  it  is  formed,  so  that  it 
is  not  possible  to  isolate  it  from  normal  blood. 

Side  by  side  with  this,  the  liver  is  exercising  its 
destructive  function  on  so  much  of  the  uric  acid  as 
may  be  brought  to  it.  The  products  of  its  action 
are  urea,  and  probably  glycine  (amino-acetic  acid). 
If  the  liver  is  largely  shut  out  of  the  circulation  by 
means  of  Eck's  fistula  (putting  the  portal  vein  into 
the  inferior  vena  cava),  uric  acid  appears  in  the  blood 
even  on  a  purin-free  diet,  because  now  so  much  of  it 
escapes  the  activity  of  the  liver  cells.  The  same 
effect  is  observed  if  the  aorta  is  tied  above  the  cceliac 
axis,  both  the  liver  and  the  kidney  being  shut  off  by 
this  operation. 

A  little  remains  to  be  said  with  regard  to  the 
endogenous  origin  of  purin  bodies.     They  are  derived 


150     THE    PHYSIOLOGY   OF    URIC   ACID 

from  two  main  sources,  the  xanthin  of  the  muscles 
and  the  nucleoprotein  of  all  cell  nuclei.  Much  of 
the  purin  bodies  split  off  from  these  is  oxidized  into 
uric  acid  by  the  above-mentioned  ferments,  but  only 
that  which  chances  to  be  carried  to  the  kidney  before 
it  reaches  the  liver  appears  in  the  urine  as  uric  acid 
or  urates.  That  which  finds  its  way  to  the  liver 
appears  in  the  urine  principally  as  urea. 

The  excretion  of  purin  bodies  on  a  purin-free  diet 
is  of  course  entirely  endogenous,  and  the  daily  output 
is  a  constant  for  the  individual,  depending  roughly 
on  the  weight  of  his  muscles.  It  is,  however, 
increased  greatly  by  muscular  exercise.  Whilst  the 
hard  work  is  proceeding  the  uric  acid  output  falls 
a  little,  while  the  xanthin  output  rises  correspond- 
ingly ;  the  muscles  take  up  so  much  oxygen  that 
there  is  none  to  spare  to  oxidize  xanthin.  After 
the  work  is  over,  the  uric  acid  rises.  Unaccustomed 
work  is  much  more  effectual  than  routine  work. 
There  is  also  a  considerable  rise  in  any  conditions 
where  cell  nuclei  are  rapidly  broken  down.  As  is 
well  known,  there  is  an  increase  of  both  uric  acid  and 
purin  bodies  in  the  urine  in  fever,  and  especially 
in  leukaemia.  In  gout,  less  uric  acid  than  usual  is 
passed. 

It  appears  that  purin  bodies  are  not  utilized  by 
the  body  in  the  synthesis  of  nucleoprotein  in  the 
protoplasm.     It  seems  to  be  formed  from  proteins. 

Indeed,  it  is  very  doubtful  if  purin  bodies  serve 
any  useful  purpose.  It  is  certain  that  they  are  power- 
ful stimulants  in  some  cases ;  caffeine  is  of  course 
one  of  the  most  powerful  and  satisfactory  stimulants 


AND    OTHER    URINARY    DEPOSITS      151 

known,  producing  a  really  increased  capacity  for 
mental  and  physical  work.  Every  one  knows  how 
a  cup  of  strong  tea,  coffee,  or  beef-tea  will  refresh  the 
weary  and  give  new  energy  to  the  student.  We  know 
that  squads  of  soldiers  doing  forced  marches  are 
greatly  helped  by  caffeine.  It  has  been  repeatedly 
proved  in  every  army  that  the  cold-tea  brigade  comes 
in  first,  the  water  men  second,  and  the  alcohol  squad 
a  bad  third.  But  we  must  set  against  this  the 
certainty  that  purin  bodies  produce  earlier  degenera- 
tion of  the  arteries,  and  occasionally  they  are 
responsible  for  very  severe  types  of  migraine. 

We  shall  not  attempt  here  to  discuss  the  difficult 
and  rather  barren  problem  of  the  pathology  of 
gout. 

We  are  now  in  a  position  to  arrive  at  some  practical 
and  clinical  deductions  from  the  work  of  the  physiolo- 
gists. An  explanation  is  furnished  of  the  appearance 
of  the  uric  acid  or  urates  deposit  in  the  urine  so 
common  in  functional  or  organic  affections  of  the 
liver ;  this  organ  is  evidently  less  active  than  usual 
in  destroying  uric  acid.  We  may  draw  the  following 
conclusions  with  regard  to  the  prevention  of  calculus 
or  gravel  in  those  threatened  with  these  complaints. 
Meat  and  broths  should  be  restricted,  also  tea,  coffee, 
and  cocoa ;  muscular  exercise  must  be  mild,  and 
warning  given  that  fever  is  dangerous.  Of  course 
if  uric  acid  crystals  tend  to  form,  plenty  of  fluid  must 
be  taken,  and  alkaline  citrates,  acetates,  or  tartrates 
given.  Salts  of  Hthium  used  to  be  preferred,  since 
Hthium  urate  is  the  most  soluble  of  the  urates,  but 
potassium  is  cheaper   and  better.      The  uric   acid 


152     THE    PHYSIOLOGY   OF    URIC   ACID 

shower  of  crystals  may  often  be  prevented  by  Gee's 
treatment,  consisting  of  a  large  cupful  of  whey  three 
times  a  day. 

A  simple  apparatus  for  determining  the  amount 
of  total  purin  in  the  urine  has  been  invented  by 
Walker  Hall.  It  is  readily  used  for  clinical  work. 
The  principle  adopted  is  to  precipitate  the  phos- 
phates with  magnesia  mixture,  then  add  ammoniacal 
silver  nitrate,  leave  standing  for  twenty-four  hours, 
and  read  the  amount  of  the  silver  purin  precipitate. 

CALCIUM     OXALATE. 

It  has  been  found  very  difficult  to  obtain  reliable 
estimates  of  oxalates  in  the  urine.  The  method 
commonly  employed,  introduced  by  Dunlop,  is  open 
to  serious  objections  from  the  chemical  standpoint. 
Working  with  O.  C.  M.  Davis,  the  writer  has  used  a 
new  and,  theoretically,  more  reliable  method,  but 
it  is  not  claimed  that  the  results  are  more  than 
approximate.  There  is  still,  therefore,  some  differ- 
ence of  opinion  as  to  the  metabolism  of  the  oxalates, 
but  the  following  conclusions  are  becoming  generally 
accepted. 

In  ordinary  circumstances,  the  whole  of  the  oxalate 
in  the  urine  is  derived  from  articles  of  food.  Milk, 
meat,  and  bread  contain  scarcely  any  oxalate  ;  most 
vegetables  contain  it,  and  rhubarb,  strawberries, 
and  sorrel  contain  a  relatively  large  quantity.  I 
have  by  taking  much  rhubarb  induced  an  attack 
of  oxaluria  sufficiently  marked  to  cause  a  good  deal 
of  smarting  pain  in  the  urethra  from  the  sharpness 
of  the  oxalate  crystals.      On  a  milk  diet,  oxalates 


AND    OTHER    URINARY    DEPOSITS      153 

disappear  from  the  urine.  This  may  be  demonstrated 
by  adding  methylated  spirit  and  allowing  to  stand, 
when  any  oxalate  present  in  solution  is  precipitated 
in  characteristic  octahedra.  On  a  milk  diet,  no  such 
crystals  will  be  obtained. 

None  of  the  ordinary  derangements  of  metabolism 
causes  the  appearance  of  oxalates  in  the  urine  if 
they  are  withheld  from  the  food.  Thus  there  is  no 
oxaluria  in  fever,  in  leukaemia  (illustrating  the 
katabolism  of  nucleoproteins),  or  in  diabetes.  In  a 
case  of  oxalic  acid  poisoning  under  my  care,  the 
excretion  was  enormous,  and  there  was  a  heavy 
deposit  of  calcium  oxalate  crystals. 

It  is  not,  however,  correct  to  say  that  oxaluria 
never  occurs  on  an  oxalate-free  diet,  though  such  a 
condition  is  rare.  As  is  well  known,  the  usual 
products  of  bacterial  fermentation  of  carbohydrates 
in  the  bowel  are  various  gases  (CH4,  C02),  lactic, 
acetic,  and  butyric  acids,  and  alcohol.  Miss  Helen 
Baldwin  has  pointed  out  that  in  certain  abnormal 
circumstances  oxalic  acid  also  may  be  formed  in  this 
way.  Copious  feeding  on  sugar  will  ruin  a  dog's 
digestion,  and  then  oxalates  may  appear  in  the  urine 
even  on  an  oxalate-free  diet.  Occasionally  she  has 
met  with  such  cases  in  man.  I  have  not  chanced  to 
observe  such  a  case  personally,  and  believe  that  they 
are  not  common. 

Fermentation  of  carbohydrates  in  the  stomach  and 
intestines  to  an  excessive  degree  is  common  enough, 
but  it  is  only  rarely  that  there  is  any  formation  of 
oxalates.  I  have  never  been  able  to  obtain  the 
crystals  either  from  the  gastric  contents  or  from  the 


154     THE    PHYSIOLOGY   OF    URIC   ACID 

urine  of  patients  with  obstruction  of  the  pylorus 
and  gastric  dilatation,  on  an  oxalate-free  diet. 

When  ammoniacal  fermentation  of  urine  takes 
place,  as  on  standing,  any  oxalate  crystals  present 
are  rapidly  dissolved  and  disappear. 

The  oxalate  calculus  is  by  far  the  most  important 
variety  occurring  in  the  kidney.  B.  Moore  has 
shown  that  a  pure  uric  acid  stone  is  found  only  in  the 
bladder,  and  that  all  renal  calculi  are  composed  for 
the  most  part  of  calcium  oxalate.  This  is  fortunate 
for  the  #-ray  diagnosis  of  the  condition,  and  as  it  is 
comparatively  easy  to  control  the  oxalate  excretion, 
it  makes  it  possible  for  us  to  advise  the  patient  how 
to  avoid  a  relapse  after  operation.  To  draw  the 
practical  lessons  from  our  study,  it  is  evident  that 
any  patient  suffering  from  oxaluria  should  abjure 
the  use  of  green  vegetables,  and  fruits  should  be 
taken  sparingly.  If  he  is  obeying  directions,  a  fresh 
specimen  of  his  urine,  mixed  with  an  equal  amount 
of  spirit  and  allowed  to  stand,  will  deposit  only  a 
few  small  crystals  of  oxalate,  and  a  specimen  without 
the  addition  of  spirit  will  show  no  crystals  even  on 
centrifugalizing.  Occasionally,  however,  one  may 
find  a  case  in  which  oxaluria  persists  even  on  a  milk 
diet.  We  must  then  restrict  the  sugars  and  starches 
of  the  diet,  and  give  remedies  calculated  to  diminish 
fermentation  in  the  stomach  and  intestines. 

If  patients  object  to  dietetic  restrictions,  potassium 
citrate  will  often  relieve,  both  by  acting  as  a  diuretic, 
and  by  making  the  urine  alkaline,  thus  dissolving 
the  crystals. 


AND    OTHER    URINARY    DEPOSITS      155 

CYSTIN. 

Cases  of  cystinuria  are  not  common.  Sometimes 
the  deposit  forms  a  yellowish-green  waxy  calculus  ; 
more  often,  flat  hexagonal  crystals  are  passed. 

In  the  chapter  on  the  digestion  and  absorption  of 
proteins,  it  was  explained  that  our  modern  conception 
of  the  molecule  is  that  of  a  long-linked  chain  of 
aminoacids,  grouped  as  monoamines,  diamines, 
and  aromatic  amines.  The  diamines  ordinarily  met 
with  in  a  protein  digest  are  called  arginin,  lysin, 
and  ornithin.  Of  this  group,  cystin  is  a  member, 
though  it  is  not  always  present  amongst  the 
products  of  protein  dissolution.  Its  formula  is 
diamino-/3-thiopropionic  acid ;  it  therefore  contains 
the  sulphur  of  the  protein  molecule.  It  has  been 
obtained  from  hair  by  chemical  disintegration. 

It  is  suggested  that  in  cases  of  cystinuria  a  physio- 
logical ferment  is  lacking  which  should  convert  the 
cystin  into  some  simpler  product.  In  a  few  of  the 
patients,  other  abnormal  diamines,  such  as  cadaverin, 
have  also  been  found  in  the  urine  ;  in  some  cases 
no  abnormal  amines  except  the  cystin  have  been 
detected.  In  a  number  of  cases  leucin  and  tyrosin 
were  being  excreted  as  well. 

Variations  in  the  diet  influence  but  little  the 
output  of  cystin  in  a  cystinuric.  Feeding  on 
arginin  (a  diamine)  or  tyrosin  (an  aromatic  amine) 
makes  no  difference.  Feeding  on  cystin  itself  merely 
increases  the  output  of  sulphates. 

Cystin  is  soluble  in  ammonia. 

It  will  be  observed  that  we  cannot  exercise  any 
useful  control  over  the  output  of  this  deposit.  It  is 
a  life-long  abnormality. 


156     THE   PHYSIOLOGY    OF   URIC   ACID 

REFERENCES. 

Uric  Acid  and  Gout. 

L.  Hill. — "  Recent  Advances  in  Physiology  and  Bio- 
chemistry," p.  387.     Arnold  &  Co.,  London,  1906. 

Von  Noorden. — "  Metabolism  and  Practical  Medicine," 
edited  by  I.  Walker  Hall,  vol.  iii,  p.  647.  Heinemann, 
London,   1907. 

Oxaluria. 

A.  Rendle  Short. — Von  Noorden's  "  Metabolism  and 
Practical  Medicine,"  vol.  i,  p.  148. 

Cystinuria. 

Garrod. — Lancet,  1908,  vol.  ii,  p.  214. 

T.  S.  Hele. — Jour,  of  Physiol.,  1909,  vol.  xxxix,  p.  52. 


157 


CHAPTER   X. 

ACIDOSIS,    ACETONEMIA,    AND 
DIABETES. 

Conditions  of  occurrence  of  acetone,  diacetic  acid,  and  /3-oxy- 
butyric  acid — Origin  from  fats — Sugar  starvation  the  cause  of 
acidosis — Acid  poisoning — The  diagnosis  of  starvation — The 
essential  nature  of  diabetes — The  treatment  of  non-diabetic 
acidosis — The  prevention  of  post-operative  coma  in  diabetics. 

TEXTBOOKS  of  medicine  published  fifteen  or 
twenty  years  ago  introduced  us  to  the  fact 
that  in  diabetic  coma,  that  tragic  termination  to  so 
many  promising  young  lives,  the  urine  is  loaded  with 
three  substances  whose  relations  were  not  well  under- 
stood— namely,  acetone,  diacetic  acid,  and  /3-oxy- 
butyric  acid.  A  constant  study  of  the  behaviour  of 
these  bodies  by  many  observers  has  led  to  some 
settled  conclusions  of  considerable  interest  and  value. 
It  has  been  shown  that  they  are  not  peculiar  to 
diabetic  coma,  although  in  no  other  disease  are  they 
excreted  in  such  quantity.  They  appear  in  the  urine 
in  the  following  conditions  also  : — 
(a).  Starvation. 

(b).  Periodic  (cyclical)  vomiting  of  children, 
(c).  Delayed  chloroform  poisoning. 
(d).  Salicylate  poisoning. 

(e).  The    toxaemias    of    pregnancy    (pernicious 
vomiting,  eclampsia). 
Starvation    may    be   voluntary,    or    due    to    such 
affections  as  gastric  ulcer,  fevers,  acute  abdominal 


158  ACIDOSIS,    ACETONEMIA, 

catastrophes,  prolonged  vomiting,  or  diarrhoea.  The 
amount  of  acetone  and  other  bodies  is  large  only  if 
the  starvation  is  prolonged. 

Cyclical  vomiting  is  a  curious  and  not  uncommon 
condition,  usually  seen  in  young  children,  who  for  a 
few  hours  or  days  at  intervals  get  bouts  of  drowsiness 
and  vomiting,  which  are  accompanied  by  the  excre- 
tion of  acetone  and  these  acids.  The  attacks  usually 
pass  off  harmlessly. 

Delayed  chloroform  poisoning  is  considered  at  some 
length  in  Chapter  XL 

It  is  known  that  an  unusual  sequence  of  overdosing 
with  salicylates  is  drowsiness  with  vomiting,  some 
collapse,  and  particularly  hissing  dyspnoea  or  air- 
hunger.  Here  again  the  above  substances  are  excreted 
in  the  urine. 

The  presence  of  acetone,  indeed,  is  perfectly 
physiological.  On  an  ordinary  diet  we  excrete  about 
O'oi  to  0*03  gram  of  acetone  daily  in  the  urine  and 
rather  more  in  the  breath,  but  these  amounts  are 
too  small  to  be  recognized  by  clinical  methods. 
During  starvation  the  excretion  by  the  seventh  day 
may  be  forty  times  as  much  (F.  Miiller).  Diacetic 
and  oxybutyric  acids  are  not  normally  present  in 
the  urine. 

ORIGIN     OF    ACETONE,    DIACETIC    ACID,    AND 
/3-OXYBUTYRIC    ACID. 

It  was  at  first  supposed  that  these  were  all  derived 
from  glucose,  because  of  their  appearance  in  diabetes  ; 
at  a  later  time  they  were  accredited  to  the  proteins ; 
but  it  is  now  definitely  established  that  they  are  the 


AND    DIABETES  159 

result  of  a  peculiar  abnormal  process  of  breaking 
down  of  the  fats. 

The  physiological  process  of  dealing  with  fat  is  to 
resolve  it  into  carbon  dioxide  and  water.  If  we 
make  a  pound  of  fat  into  tallow  candles  and  burn  it, 
wre  shall  obtain  carbon  dioxide  and  water,  and  a 
certain  amount  of  heat  will  be  evolved.  If  the  pound 
of  fat  is  eaten  and  absorbed  by  a  man  or  an  animal,  it 
will  be  burnt  to  the  same  end-products,  and  the  same 
amount  of  heat  will  be  given  out.  But  in  certain 
circumstances,  an  abnormal  mode  of  breaking  down 
is  followed,  and  there  are  produced  first  /3-oxybutyric 
acid,  then  diacetic  acid,  and  finally  acetone.  If  this 
takes  place  on  a  large  scale,  the  conversion  into 
acetone  fails  to  keep  pace  with  the  production  of  the 
acids.  Therefore  first  acetone  appears  in  the  urine, 
then  diacetic  acid,  and  finally  /3-oxybutyric  acid  ; 
the  last  may  rise  rapidly  to  an  enormous  figure  :  30, 
50,  or  even  180  grams  may  be  passed  daily  in  dia- 
betic coma  (Magnus  Levy). 

Feeding  on  fats  will  always  cause  some  rise  in  the 
output  of  acetone  and  of  these  acids  if  they  are  already 
present ;  in  starvation  it  will  cause  a  very  marked 
increase.  Butter,  which  contains  lower  fatty  acids 
(butyric,  etc.),  as  well  as  fats,  is  particularly  active  in 
this  respect. 

It  is  of  no  great  importance  to  us  to  know  where 
in  the  body  this  process  of  breaking  down  takes  place  ; 
the  liver  is  usually  supposed  to  have  the  power  to 
effect  it. 

We  next  ask,  What  are  the  special  circumstances 
in  which  the  breaking   down  of  fat  deviates  from 


160  ACIDOSIS,     ACETONEMIA, 

its  normal  course,  and  follows  this  dangerous  route  ? 
The  answer  is  clear  and  decisive.  When  the  tissues 
are  unable  to  obtain  sugar  from  the  blood,  fat  is  broken 
down  via  these  abnormal  acids  to  acetone,  instead  of  to 
carbon  dioxide  and  water. 

This  remarkable  proposition  has  been  abundantly 
proved,  and  along  several  independent  lines  of 
research.  Thus  in  one  case,  an  experimenter  (Satta) 
ate  nothing  for  two  days  but  milk  sugar,  and  excreted 
the  normal  amount  of  o#oi  gram  of  acetone  daily. 
Then  he  took  a  diet  of  300  grams  each  of  meat  and  fat, 
which  is  of  course  quite  an  adequate  amount  to 
sustain  health,  and  the  excretion  rose  to  o*8  gram 
and  i'i  gram  on  the  two  days  of  experiment.    Thus  : 

Day  1.  Diet  only  lactose.  Excreted  o-oi  grrn.  acetone. 

Day  2.         „       „         „  „       o-oi     „ 

Day  3.         ,,     meat  and  fat  ,,       o*8o     „  ,, 

Day  4.         „  „         „  „       i-io     „ 

As  we  shall  see,  if  the  tissues  can  be  supplied  with 
glucose,  pathological  acetonemia  and  acidosis  are 
rapidly  cured. 

It  now  becomes  evident  why  acetone  and  the  acids 
are  formed  in  the  conditions  above  referred  to.  In 
starvation  the  tissues  cannot  obtain  glucose  because 
there  is  none  in  the  blood.  In  cyclical  vomiting  of 
children,  and  in  delayed  chloroform  poisoning,  the 
conditions  are  a  little  more  complex.  Mild  aceton- 
emia is  set  up  in  the  first  place  either  by  abstinence 
from  carbohydrate  food  for  a  longer  time  than  usual, 
or  by  some  toxic  agent  preventing  the  tissues  from 
obtaining  the  requisite  sugar  for  the  blood  by  para- 
lysing   in    some    way    their    activity ;     in    many 


AND    DIABETES  161 

cases  both  these  causes  are  combined,  as  when  a 
patient  with  a  perforated  gastric  ulcer,  who  has 
absorbed  nothing  for  hours,  is  given  chloroform. 
The  vomiting  induced  by  the  acetonemia  of  course 
prevents  the  retention  of  carbohydrate  food,  and  so 
the  bad  becomes  worse. 

Salicylates  presumably  act  by  paralysing  that 
function  of  the  tissues  which  enables  them  to  take 
up  sugar  from  the  blood.  As  we  shall  see,  this  is 
also  the  pathology  of  diabetes.  The  tissues,  starved 
of  sugar,  break  down  the  fat  to  acids  and  acetone 
instead  of  to  carbon-  dioxide  and  water.  With 
reference  to  the  acidosis  of  pregnancy,  some  un- 
published observations  by  Statham,  made  at  the 
Bristol  Royal  Infirmary,  show  that  in  addition  to 
the  acidosis  of  pernicious  vomiting,  in  which  probably 
starvation  is  a  factor,  there  is  constantly  an  increase 
in  the  ammonia  nitrogen  ratio  in  the  urine  in  the 
pre-eclamptic  state  as  well  as  in  eclampsia  ;  usually 
there  is  di acetic  acid  present,  but  not  always.  If 
the  patient  is  kept  on  glucose,  the  nitrogen  ratio 
becomes  normal  soon  after  delivery,  but  not  before. 

THE  MECHANISM  OF  POISONING  IN  ACIDOSIS 
AND    ACETONEMIA. 

Neither  acetone,  diacetic  acid,  nor  /3-oxybutyric 
acid  is  poisonous,  except  in  enormous  doses.  Why 
then  do  such  marked  and  indeed  fatal  symptoms 
occur  when  they  accumulate  ? 

The  blood  is  normally  alkaline.  All  the  functions 
of  the  tissues  are  attuned  to  a  medium  of  a  particular 
alkalinity.     If    this    alkalinity    is    greatly    reduced, 

ii 


162  ACIDOSIS,     ACETONEMIA, 

almost  to  a  point  of  neutralization,  the  symptoms 
produced  experimentally  are  not  dependent  on  the 
particular  acid  used.  They  include  dyspnoea,  vomit- 
ing, and  coma.  In  diabetic  coma  the  alkalinity  of  the 
blood  is  much  reduced  by  the  increase  of  diacetic 
and  especially  of  /3-oxybutyric  acids  in  the  plasma. 
This  condition  is  called  "  acidosis."  It  would 
perhaps  be  going  too  far  to  say  that  absolutely 
unlimited  quantities  of  /3-oxybutyric  acid  may  be 
formed  and  tolerated  if  sufficient  alkali  is  supplied 
to  neutralize  it ;  there  is  a  point  beyond  which 
even  sodium  /3-oxybutyrate  becomes  toxic ;  and  by 
keeping  the  urine  alkaline,  although  we  may  greatly 
delay,  we  do  not  altogether  prevent  the  onset  of  dia- 
betic coma. 

The  body  is  able  for  a  long  time  to  defend  itself 
against  the  increased  production  of  diacetic  and 
/3-oxybutyric  acids,  by  furnishing  enough  alkali  to 
neutralize  them  more  or  less  completely.  First, 
the  reserves  of  sodium  and  potassium  are  called  upon, 
but  the  main  defence  is  the  production  of  large 
quantities  of  ammonia.  In  normal  metabolism  the 
proteins  of  the  tissues  split  off  their  effete  nitrogen 
in  the  form  of  ammonium  salts  (carbonate,  carbamate, 
etc.),  and  these  are  converted  into  urea  by  the  liver. 
When  diacetic  and  /3-oxybutyric  acids  are  present, 
these  unite  with  the  ammonia,  and  it  escapes  con- 
version into  urea  ;  consequently  there  will  be  an 
increase  of  ammonia  nitrogen  in  the  urine  (as  am- 
monium diacetate  and  ammonium  /3-oxybutyrate).  At 
length,  however,  the  production  of  the  acids  becomes 
so  excessive  that  the  supply  of  ammonia  from  the 


AND     DIABETES  163 

tissues  fails  to  keep  up  with  them.  Then  the  normal 
alkalinity  of  the  blood  falls,  and  dyspnoea,  collapse, 
and  coma  begin  to  appear. 

DIAGNOSIS    OF    STARVATION. 

It  may  become  very  important  to  know  if  a  patient 
is  or  is  not  obtaining  adequate  nourishment.  This 
is  particularly  the  case  when  on  account  of  vomiting, 
haematemesis,  or  typhoid  fever,  mouth  feeding  has 
to  be  restricted  or  becomes  altogether  impossible. 
It  is  easy  to  find  out.  Daily  estimates  of  the  urea 
output  will  show  if  the  protein  absorbed  is  adequate, 
and  tests  for  acetone,  diacetic  acid,  and  oxybutyric 
acid  will  show  if  the  supply  of  carbohydrate  has 
fallen  too  low.  The  normal  ratio  of  ammonia 
nitrogen  to  urea  nitrogen  is  about  5  per  cent.  If  it 
rises  to  10,  15,  or  20  per  cent,  there  is  severe  acidosis 
present,  due  to  starvation,  but  masked  by  the  am- 
monia supplied  to  neutralize  it.  When  the  supply  of 
ammonia  fails,  fatal  coma  will  follow. 

THE  ESSENTIAL  NATURE  OF  DIABETES. 

Seeing  that  it  is  in  diabetics  that  the  most  terrible 
consequences  of  acidosis  are  exhibited,  it  will  be 
well  very  briefly  to  consider  just  in  what  way  the 
metabolism  has  gone  wrong  in  this  disease. 

Glycosuria  may  be  experimentally  induced  in 
animals  by  the  following  means  : — 

(a).  By  puncture  of  the  medulla. — This  is  perhaps 
a  vasomotor  effect,  the  increased  blood-flow  washing 
glycogen  out  of  the  liver.  Or  there  may  be  some 
interference    with    secretory    nerves    to    the    liver. 


164  ACIDOSIS,     ACETONEMIA, 

Stimulation  of  the  central  end  of  the  divided  vagus 
acts  in  the  same  way.  To  this  class  belong  those 
clinical  cases  in  which  transient  glycosuria  follows 
head  injury  or  cerebral  compression. 

(b).  By  very  excessive  feeding  on  sugars. — Doses  of 
over  150  grams  of  glucose  or  cane  sugar  will  set  up 
a  sort  of  overflow  glycosuria  ;  smaller  quantities  of 
lactose  or  maltose  (from  beer)  will  do  the  same. 

(c).  By  administration  of  phloridzin,  which  is  a 
glucoside  occurring  in  the  bark  of  plum  and  cherry 
trees.  This  drug  has  the  remarkable  power  of  com- 
pelling the  secretory  epithelium  of  the  kidney  to 
break  down  serum-albumin  so  as  to  yield  sugar  ; 
the  glycosuria  is  not  therefore  associated  with  £tny 
increase  of  sugar  in  the  blood. 

It  is  of  course  conceivable  that  human  diabetes, 
in  some  cases  at  least,  might  be  of  renal  origin  in  a 
similar  manner,  and  an  attempt  has  actually  been 
made  in  France  to  separate  off  a  class  of  renal  dia- 
betics, but  very  few  English,  German,  or  American 
authorities  allow  the  justifiability  of  this.  Phloridzin 
glycosuria  would  be  devoid  of  practical  interest  if  it 
were  not  that  it  has  recently  been  taken  up  by  the 
surgeon  for  diagnostic  purposes.  When  a  patient 
has  severe  tuberculosis  of,  shall  we  say,  the  right 
kidney,  but  the  condition  of  the  left  is  doubtful,  it 
would  of  course  be  a  serious  risk  to  remove  the  right 
kidney,  and  indeed  a  fatal  result  has  several  times 
been  recorded.  Of  the  methods  of  investigating 
the  function  of  the  left  kidney,  one  of  the  best  is  to 
give  phloridzin.  If  sugar  fails  to  appear  in  the  urine, 
both   kidneys    are    seriously    diseased ;      if   it    does 


AND    DIABETES  165 

appear,  there  is  still  an  efficient  amount  of  renal 
substance.  To  give  precision  to  the  test  it  is  usually 
wise  to  catheterize  both  ureters,  and  to  analyse  the 
urines  separately. 

(d.)  By  variations  in  the  blood-content  of  C02. — 
Apparently  either  a  marked  rise  or  a  marked  fall  in 
the  amount  of  carbon  dioxide  in  the  blood  may 
produce  glycosuria.  Prolonged  deep  breathing,  for 
instance,  reduces  the  C0.2  in  the  blood  to  a  very  low 
figure,  and  not  infrequently  transient  glycosuria 
results.  This  has  been  adduced  as  the  explanation 
of  its  occurrence  after  violent  anger  or  after  anaes- 
thetics. Strong  saline  injections  may  also  induce 
glycosuria. 

(e).  The  ductless  glands  and  diabetes.— There  is 
probably  an  important  and  complicated  relationship 
between  the  ductless  glands  and  glycosuria.  So  far 
we  only  know  a  few  isolated  facts.  Thus,  adrenalin 
injection  causes  glycosuria  of  pancreatic  type  ;  in 
hyperthyroidism  sugar  may  appear  in  the  urine  and 
the  toleration  limit  of  glucose  may  be  very  low  (less 
than  ioo  grams  may  set  up  glycosuria)  ;  on  the  other 
hand,  partial  excisions  of  the  pituitary  gland  raise 
the  toleration  for  glucose  above  the  normal  150 
grams. 

(  / ).  Pancreatic  diabetes. — Removal  of  the  pancreas 
in  dogs  or  other  animals  if  complete  induces  fatal 
diabetes  exactly  corresponding  to  severe  cases  of  the 
disease  in  man  ;  a  sub-total  removal  brings  about  a 
milder  type  of  the  disease.  The  symptoms  are 
improved  by  pancreatic  grafting.  If  less  than  four- 
fifths  of  the  pancreas  is  taken  away,  no  glycosuria 


166  ACIDOSIS,     ACETONEMIA, 

follows.  After  complete  removal,  but  not  after 
removal  of  four-fifths,  sugar  will  continue  to  appear 
in  the  urine  even  when  all  carbohydrates  are  excluded 
from  the  food,  being  derived  in  this  case  from  the 
breaking  down  of  food  and  body  protein. 

In  ordinary  human  diabetes,  the  pancreas  is  found 
at  autopsy  to  present  some  abnormality  in  such  a 
large  proportion  of  cases  that  the  smaller  group  in 
which  nothing  is  found  amiss  may  safely  be  attributed 
to  functional  deficiency  apart  from  organic  disease. 
To  quote  an  analogy,  mental  defect  is  so  often 
associated  with  gross  changes  in  the  brain  that  we 
think  we  are  justified  in  assuming  that  there  must  be 
some  functional  derangement  of  that  organ,  even  when 
in  cases  of  insanity  it  appears  to  be  quite  normal. 

In  what  way  may  destruction  of  the  pancreas 
conceivably  produce  diabetes  ? 

The  present-day  teaching  is  that  the  pancreas 
supplies  to  the  blood  some  internal  secretion,  some 
chemical  substance,  which  is  carried  to  the  muscles 
and  other  tissues  to  enable  them  to  make  use  of  the 
sugar  brought  them  by  the  blood.  The  tissues  are 
positively  in  need  of  sugar.  It  is  probably  an  essential 
source  of  muscular  energy.  A  beating  mammalian 
heart,  through  which  a  solution  of  salines  containing 
sugar  is  repeatedly  passed,  will  use  up  that  sugar. 
It  is  a  principal  source  of  heat.  It  is  probably  a 
necessity  for  nearly  all  the  functions  of  the  proto- 
plasm of  the  tissues.  The  blood  always  contains 
sugar  (about  o*i  per  cent)  to  supply  this  need  ;  the 
whole  process  of  glycogen-storing  in  the  liver  is 
designed  to  keep  the  percentage  at  a  constant  level 


AND    DIABETES  167 

in  the  blood.  The  internal  secretion  of  the  pancreas 
is  the  link  whereby  the  tissues  may  take  hold  of  and 
utilize  this  circulating  sugar.  In  diabetes  the  internal 
secretion  of  the  pancreas  fails,  and  the  link  is  missing. 
The  tissues  are  in  the  position  of  the  hungry  boy 
outside  the  sweet-shop  ;  he  longs  for  the  sweets  and 
the  supply  is  abundant,  but  he  has  not  the  means  to 
purchase.  So  the  sugar  in  the  blood,  lacking  a 
market,  goes  on  accumulating  till  it  reaches  a  figure 
of  0'2  or  03  per  cent ;  it  runs  to  waste  in  the  urine, 
but  the  tissues  cannot  touch  it.  Like  a  starving  town 
through  which  rich  convoys  are  passing,  the  plenty 
comes  to  their  very  doors,  but  cannot  be  utilized. 
Urgent  messages  for  food  are  sent  to  the  liver,  to  other 
organs,  to  the  intestine  ;  these  are  depleted  of  all  their 
reserves  of  glycogen,  and  even  the  proteins  themselves 
are  broken  down  wastefully  to  obtain  sugar,  some  of 
which  slips  out  into  the  blood  and  is  permanently 
lost  to  the  tissues.  So  we  see  the  patient  losing 
flesh,  and  not  only  sugar  but  also  excess  of  urea 
appear  in  the  urine,  derived  of  course  from  the 
proteins. 

Naturally,  in  most  cases  matters  have  not  progressed 
quite  so  far  ;  a  little  of  the  pancreatic  secretion  con- 
tinues to  be  supplied,  and  if  carefully  husbanded, 
as  by  reducing  the  carbohydrate  in  the  food,  may 
suffice  for  the  bare  needs  of  the  body.  To  return  to 
the  illustration,  the  hungry  boy  is  not  quite  penniless, 
and  if  he  spends  his  money  wisely  he  may  yet  keep 
himself  going  by  alternating  periods  of  self-denial 
and  mild  indulgence. 

It  must  be  admitted  that  some  researches  of  the 


168  ACIDOSIS,     ACETONEMIA, 

past  few  months  have  taught  us  to  be  cautious  in 
coming  to  the  conclusion  that  the  problems  of 
diabetes  are  solved.  A  year  or  two  ago  Starling  and 
Knowlton  advanced  what  appeared  to  be  most 
interesting  evidence,  that  after  removal  of  trie 
pancreas  the  surviving  beating  heart  of  a  dog  is 
unable  to  make  use  of  dextrose  perfused  through  it, 
but  that  if  pancreatic  extract  is  added,  the  power  to 
utilize  sugar  is  restored.  This  of  course  exactly 
fitted  the  theory.  But  now  Starling  finds  that  the 
supposed  results  were  due  to  experimental  error, 
and  that  the  diabetic  heart  is  well  able  to  use  up 
sugar. 

Various  authorities  have  tried  to  go  further  with 
the  explanation  of  human  diabetes,  and  have  stated 
that  the  internal  secretion  is  derived  from  the  clusters 
of  cells  called  islets  of  Langerhans,  whereas  the 
digestive  juices  are  derived  from  the  acini ;  it  has 
further  been  stated  that  in  diabetes  sometimes  the 
islets  are  destroyed  whilst  the  rest  of  the  pancreas  is 
normal.  Ligature  of  the  pancreatic  duct  causes 
atrophy  of  the  secreting  cells  of  the  alveoli,  but  not 
the  islets,  and  is  not  followed  by  glycosuria.  Some 
observations  by  Dale,  supposed  to  tell  against  the 
theory,  are  not  confirmed.  It  is  true  that  in  some 
cases  of  human  diabetes  the  islets  appear  to  be 
normal.  Perhaps  we  must  look  to  some  alteration 
in  the  internal  secretions  of  the  ductless  glands  for 
an  explanation  of  these  cases. 

Again,  such  wide  currency  has  been  given  to  an 
experiment  of  Cohnheim's,  that  it  is  necessary  to 
state  and  refute  it.     He  taught  that  muscle  extract 


AND    DIABETES  169 

with  pancreatic  extract  was  able  to  break  down 
sugar,  but  that  neither  was  able  to  do  so  without 
the  other.  It  has  since  been  abundantly  proved 
that  muscle  extract  can  break  down  sugar  just  as  well 
by  itself.  Von  Noorden  considers  that  the  pancreatic 
secretion  is  necessary  to  enable  the  tissues  to  build 
up  sugar  (C6H1206)  into  the  more  complex  glycogen 
(C6H1(J05)n,  where  the  n  may  stand  for  a  very  high 
figure  ;  glycogen  he  takes  to  be  a  necessary  stage  in 
the  absorption  of  sugar  into  the  molecule  of  proto- 
plasm. Certain  it  is  that  both  in  experimental  and 
human  diabetes,  glycogen  is  absent  from  the  liver 
and  muscles  in  all  but  mild  cases. 

Returning  to  the  question  of  acidosis  in  diabetes, 
we  are  now  able  to  understand  why  it  is  so  marked 
and  so  fatal  an  occurrence.  We  saw  that  the  cause  of 
acidosis  was  the  failure  of  the  tissues  to  obtain  sugar. 
Obviously  severe  diabetes  will  be  a  far  more  potent 
factor  in  leading  up  to  this  condition  than  even 
starvation.  And  indeed,  of  severe  cases  of  diabetes, 
that  is,  cases  in  which  complete  deprivation  of 
carbohydrate  food  will  not  abolish  the  glycosuria, 
about  four-fifths  die  in  coma.  Most  of  us  have  known 
instances.  It  may  have  been  a  young  man  or  woman, 
the  victim  of  diabetes  certainly,  but  otherwise 
apparently  in  good  health,  with  only  the  fatal  red 
fringe  on  touching  the  urine  with  ferric  chloride  to 
hold  out  any  warning.  There  was  a  long  walk,  a 
feverish  cold,  an  anaesthetic  ;  or  some  physician  too 
suddenly  instituted  a  severe  deprivation  of  carbo- 
hydrate food,  and  within  a  few  hours  coma  had  set 
in,  and  death  was  inevitable. 


170  ACIDOSIS,    ACETONEMIA, 

THE    TREATMENT  OF    NON-DIABETIC 
ACIDOSIS. 

It  will  probably  be  agreed  that  the  time  has  now 
come  when  no  examination  of  the  urine  in  cases  of 
diabetes,  of  abdominal  catastrophes,  of  vomiting,  or 
of  starvation,  will  be  complete  unless  we  record  the 
presence  or  absence  of  acetone  and  diacetic  acid  as 
well  as  of  albumin  and  sugar.  Unfortunately  there 
is  no  simple  clinical  test  for  /3-oxybutyric  acid.  It 
has  been  usual  to  estimate  it  by  the  amount  of 
lsevo-rotation  of  a  ray  of  polarized  light,  from  which 
of  course  must  be  deducted  the  dextro-rotation  due 
to  any  glucose  which  may  be  present. 

A  fairly  simple  qualitative  test  is  Stuart-Hart's  : 
Take  20  c.c.  of  urine,  add  20  c.c.  of  water  and  a  few 
drops  of  acetic  acid.  Boil  the  mixture  till  the  bulk 
is  reduced  to  about  10  c.c.  ;  thus  acetone  and  diacetic 
acid  are  driven  off.  Add  water  to  restore  the  bulk 
to  20  c.c.  ;  put  10  c.c.  into  each  of  two  test-tubes,  A 
and  B.  To  A  add  1  c.c.  of  hydrogen  peroxide ;  just 
warm  it,  but  do  not  boil,  for  one  minute.  Cool. 
Add  to  A  and  B  J  c.c.  of  glacial  acetic  acid,  a  few 
drops  of  fresh  sodium  nitroprusside,  and  overlay  with 
2  c.c.  of  ammonium  hydrate.  Stand  four  hours.  If 
/3-oxybutyric  acid  was  present,  it  will  have  been 
oxidized  to  acetone,  and  a  purple-red  ring  will  form 
where  the  fluids  meet  in  A,  but  not  in  B.  The 
presence  of  sugar  does  not  interfere  with  the 
reaction. 

The  presence  of  acetone  cannot  be  definitely 
excluded  without  distilling  the  urine,  but  too  delicate 
tests  are  usually  less  valuable  than  more  approximate 


AND    DIABETES  171 

ones,  because,  as  in  this  instance,  a  trace  may  be 
found  normally.  The  presence  of  diacetic  acid  is  of 
more  clinical  importance. 

Tests  for  acetone  in  the  urine  : — To  3  c.c.  of  urine 
add  a  few  drops  of  fresh  sodium  nitroprusside  (a 
crystal  in  5  c.c.  of  water).  Cover  with  strong  ammonia. 
A  magenta  ring  appears  at  the  line  of  junction,  and 
spreads  upwards  (Jackson-Taylor).  Or,  to  5  c.c.  of 
urine  add  J  c.c.  of  5  per  cent  sodium  nitroprusside  ; 
make  just  alkaline  with  caustic  soda,  and  acidify 
with  acetic  acid.  A  reddish-violet  colour  develops. 
Diacetic  acid  also  gives  this  test. 

Acetone  is  excreted  in  the  breath  as  well  as  in  the 
urine,  and  the  sweet  odour  is  perfectly  apparent  to 
many  medical  men,  more  so  to  some  than  others  ; 
some  can  smell  a  diabetic  excreting  acetone  at  a  great 
distance.  It  is  remarkable  how  the  flies  may  con- 
gregate about  a  diabetic  in  a  ward. 

Test  for  diacetic  acid  in  the  urine  : — To  3  c.c.  of 
urine  add  a  few  drops  of  liq.  ferri  perchlpr.  A 
deep  red  colour  which  disappears  on  heating  is 
positive.  The  test  is  often  performed  on  a  white 
slab  as  a  contact  test.  One  must  not  be  deceived 
by  the  frequent  reddish  precipitate  of  iron  phosphate 
from  a  normal  urine. 

Turning  now  to  the  prevention  and  treatment  of 
acidosis,  we  may  clear  the  ground  by  reserving 
diabetic  coma  for  a  special  word  later  on  in  the 
chapter,  and  delayed  chloroform  poisoning  for  con- 
sideration in  Chapter  XL 

We  saw  that  the  cause  of  this  peculiar  perversion 
of  metabolism  is  inability  on  the  part  of  the  tissues 


172  ACIDOSIS,     ACETONEMIA, 

to  obtain  sugar,  and  that  the  fatal  element  in  the 
poisoning  is  the  swamping  of  the  blood  with  acids. 
Therefore  prevention  lies  in  the  supply  of  glucose, 
and  treatment  is  to  introduce  alkalies.  In  practice, 
as  might  be  expected,  glucose  alone  is  better  than 
alkalies  alone  ;  probably  both  together  would  give 
the  best  results. 

On  account  of  vomiting  it  may  not  be  possible  to 
administer  either  by  the  mouth.  They  may  be  given 
by  the  rectum,  or  directly  into  a  vein.  If  the  case  is 
urgent,  the  latter  method  would  be  adopted  ;  if  not, 
the  former.  Glucose  should  be  given  in  either  case 
in  6  per  cent  solution  in  warm  distilled  water,  using 
two  or  three  pints.  Sodium  carbonate  may  be  given 
in  doses  of  4  drachms  to  the  pint,  again  using  two  to 
three  pints.  It  should  be  the  object  of  the  treatment 
to  make  the  urine  alkaline. 

In  milder  cases,  it  will  of  course  be  possible  to 
give  remedies  by  the  mouth.  The  addition  of  enough 
starch  or  sugar  to  bring  the  daily  supply  of  carbo- 
hydrate up  to  150  grams  (5  ounces)  will  effectually 
banish  the  pernicious  acids  in  the  urine.  Alkalies 
are  best  given  in  the  form  of  sodium  citrate,  30  grains 
or  more  three  times  a  day,  until  the  urine  is  alkaline. 

It  is  important  to  bear  in  mind  the  danger  of  this 
auto-intoxication,  that  is,  poisoning  by  the  products 
of  the  patient's  own  internal  processes,  in  all  the 
numerous  conditions  in  which  insufficient  food  may 
be  absorbed,  so  that  serious  or  fatal  symptoms  may 
be  warded  off.  Diarrhoea,  wasting,  or  vomiting, 
from  whatever  cause,  should  lead  to  an  examination 
of  the  urine  for  diacetic  acid,  and  the  same  is  specially 


AND    DIABETES  173 

necessary  when  a  patient  is  being  fed  only  by  the 
rectum. 

The  old-fashioned  treatment  of  rheumatic  fever, 
by  combining  alkalies  with  the  salicylates,  will 
prevent  acidosis  from  the  use  of  the  latter. 

The  Prevention  of  Diabetic  Coma. — In  the  treat- 
ment of  a  severe  case  of  diabetes  the  physician  is 
on  the  horns  of  a  dilemma.  To  relieve  the  ordinary 
symptoms  of  diabetes,  which  are  due  to  the  excess  of 
sugar,  and  to  enable  the  patient  to  make  the  best 
possible  use  of  what  little  internal  secretion  of  the 
pancreas  he  has  left,  the  indications  are  to  reduce  or 
exclude  the  carbohydrates  from  the  food,  replacing 
them  by  fats  and  proteins.  To  prevent  the  formation 
of  the  abnormal  acids  from  fat  in  the  absence  of 
available  sugar,  the  indications  are  to  reduce  the  fats 
and  to  supply  carbohydrates.  The  one  has  to  be 
weighed  against  the  other. 

The  general  treatment  of  diabetes  is  not  dis- 
cussed here.  The  writer  has  neither  the  space  nor  the 
special  experience  which  would  be  necessary.  We 
shall  confine  ourselves  to  the  physiological  problem 
of  averting  diabetic  coma. 

Let  it  be  an  axiom  that  no  case  of  diabetes  is 
suddenly  to  be  put  on  a  carbohydrate-free  diet  on 
first  acquaintance.  Particularly  would  this  be  dan- 
gerous if  he  already  had  diacetic  and  /3-oxybutyric 
acids  in  the  urine.  If  they  are  absent,  that  is,  if  there 
is  no  red  colour  on  bringing  the  urine  into  contact  with 
ferric  chloride,  a  strict  diet  will  be  safe  and  valuable. 

It  would  be  going  too  far  to  say  that  severe  limita- 
tion of  the  carbohydrates  is  never  indicated  when 


174  ACIDOSIS,     ACETONEMIA, 

diacetic  acid  is  present.  Von  Noorden  has  a  daily 
quantitative  analysis  made  of  the  excretion  of 
/3-oxybutyric  acid,  and  with  this  safeguard,  which 
of  course  involves  a  complicated  procedure,  strict 
dieting  is  often  safe.  Patients  with  the  acids  in  the 
urine  may  live  for  many  years. 

Apart  from  an  analysis  of  the  excretion  of  /3-oxy- 
butyric acid,  it  will  usually  be  justifiable  to  limit  the 
carbohydrates,  provided  that  the  patient  is  carefully 
watched  for  any  slight  drowsiness,  vomiting,  or  air- 
hunger,  and,  further,  that  the  urine  is  kept  alkaline 
with  sodium  citrate.  Fortunately,  feeding  diabetics 
on  fat  does  not  greatly  increase  the  excretion  of 
acetone  bodies,  if  the  lower  fatty  acids  in  butter  are 
washed  out  with  cold  water  before  it  is  taken. 

When  there  is  severe  acidosis,  as  evidenced  by  the 
quantity  of  diacetic  and  /3-oxybutyric  acids  in  the 
urine,  or  when  there  are  threatening  symptoms  such 
as  a  little  tendency  to  drowsiness  or  vomiting,  it  is 
necessary  at  all  costs  to  get  in  carbohydrate  at  once. 
The  most  effectual  method  of  doing  so,  and  one  which 
only  very  slightly  increases  the  glycosuria,  is  to  adopt 
von  Noorden's  oatmeal  treatment.  He  allows  nothing 
for  three  or  four  days  but  seven  or  eight  ounces  of 
oatmeal,  given  as  gruel  every  two  hours,  with  butter, 
eggs,  and  vegetable  protein,  tea,  coffee,  wine,  or 
whisky.  Then  for  a  day  or  two  he  gives  nothing 
but  vegetables. 

The  effect  on  the  acidosis  is  usually  very  marked, 
the  ferric  chloride  reaction  disappearing  in  a  few 
days.  The  glycosuria  also  may  improve  to  a  con- 
siderable extent.     It  is  extraordinary  that  so  much 


AND    DIABETES  175 

starch  as  the  oatmeal  contains  should  not  make  the 
glycosuria  worse,  but  apparently  it  does  not  do  so. 
A  diet  restricted  to  potatoes  may  have  the  same 
beneficial  effect. 

At  the  same  time,  alkalies  should  of  course  be 
administered,  either  by  mouth,  rectum,  or  intra- 
venously. 

It  may  be  asked,  Of  what  avail  is  it  to  give  carbo- 
hydrates, when  the  tissues  will  not  be  able  to  make 
use  of  them  owing  to  the  absence  of  the  internal 
secretion  of  the  pancreas  ?  If  the  internal  secretion 
were  actually  absent,  the  case  would  of  course  be 
beyond  treatment,  but  there  is  always  hope  that  a 
little  may  still  be  available  to  assist  in  the  assimilation 
of  glucose  by  the  protoplasm ;  and  if  the  sugar  has 
been  expelled  from  the  blood  by  severe  dieting,  so 
that  acidosis  has  resulted,  the  administration  of 
carbohydrate  may  save  the  situation. 

Again,  it  may  be  asked,  Why  not  give  extract  of 
pancreas  as  a  drug  ?  Unfortunately,  it  has  been 
thoroughly  tried  and  has  failed.  Most  probably  the 
active  principle  is  either  destroyed  by  digestion  or 
is  not  absorbed  from  the  bowel.  Pancreatic  grafting 
gives  some  temporary  relief  in  animals. 

It  is  well  known  that  diabetic  coma  may  be  pre- 
cipitated by  a  surgical  operation.  In  some  cases 
matters  are  so  urgent  that  there  is  no  time  for 
precautions  to  be  taken  to  avoid  this  calamity,  but 
if  a  day  or  two  can  be  secured  first,  it  should  be 
possible  with  our  present  knowledge  to  banish  this 
bugbear  from  surgery.  It  will  be  much  safer  to  give 
ether  than  chloroform,  on  account  of  the  danger  of 


176    ACIDOSIS,    ACETONEMIA,    DIABETES 

delayed  chloroform  poisoning.  If  the  urine  con- 
tains no  diacetic  acid  this  precaution  will  be  sufficient. 
Should  the  red  coloration  with  ferric  chloride  be 
present,  however,  the  patient  ought  to  be  put  on  the 
oatmeal  diet,  and  alkalies  introduced  by  mouth, 
rectum,  or  intravenously,  until  the  acid  reaction  of 
the  urine  disappears.  These  measures  must  be  kept 
up  for  a  day  or  two  after  the  operation,  until  the 
danger  has  passed. 

Perhaps  we  are  scarcely  yet  entitled  to  speak  of  the 
treatment  of  diabetic  coma.  It  is  true  that  after 
intravenous  injection  of  two  or  three  pints  of  a 
solution  of  sodium  carbonate  (3iv  to  the  pint), 
patients  have  made  a  marvellous  rally,  and,  as  in 
one  case  in  the  writer's  experience,  may  be  so  far 
recovered  as  to  sit  up  in  bed,  eat  an  orange  (without 
leave),  and  talk  to  friends.  But  the  symptoms  soon 
recur,  and  proceed  to  a  fatal  termination.  The 
alkaline  injection  must  not  be  given  subcutaneously, 
but  intravenously  ;  the  former  method  will  often 
cause  gangrene. 

REFERENCES. 

L.  Hill. — "  Recent  Advances  in  Physiology  and  Bio- 
chemistry," Arnold  &  Co.,  London,  1906,  p.  312. 

Von  Noorden. — "  Metabolism  and  Practical  Medicine," 
Heinemann    &    Co.,    London,    1907.  Edited    by    I. 

Walker  Hall.  Vol.  i,  p.  169  (Acetone  Bodies)  ;  vol.  iii, 
(Diabetes  Mellitus). 

Von  Noorden. — "  Diabetes  Mellitus,"  J.  Wright  &  Sons  Ltd., 
Bristol,  1906  ;  "  Acid  Auto-intoxications,"  J.  Wright 
&  Sons  Ltd.,  Bristol,  1904. 

Starling. — Jour,  of  Physiol.,   191 3,  October. 


177 


CHAPTER   XL 

IMMEDIATE    AND    REMOTE    POISONING 
BY     CHLOROFORM. 

Sudden  death  under  chloroform — The  fatal  adrenalin-chloroform 
combination — Delayed  chloroform  poisoning. 

ENTHUSIASTIC  advocates  of  chloroform  as  the 
ideal  anaesthetic  (usually  hailing  from  the 
north)  used  to  say,  "  Chloroform  kills  your  patient 
to-day,  and  ether  kills  him  to-morrow."  They 
referred  of  course  to  the  pulmonary  complications 
which  used  to  follow  the  use  of  the  latter  drug  in  the 
days  when  it  was  given  by  a  Clover's  inhaler  through- 
out the  operation,  instead  of  by  the  open  method. 
We  are  now  finding  out  that  chloroform  too  may  not 
claim  its  victims  until  to-morrow. 

Chloroform  may  cause  a  fatality  in  three  distinct 
ways  :  first,  by  sudden  arrest  of  the  heart ;  secondly, 
by  poisoning  the  heart  and  vital  centres  in'  the 
medulla  of  the  brain  ;  and  thirdly,  by  inducing  acute 
fatty  degeneration  of  the  viscera,  and  acidosis.  We 
shall  here  only  consider  the  first  and  third. 

SUDDEN  ARREST  OF  THE  HEART. 

Some  of  the  most  tragic  calamities  of  surgical 
practice  are  due  to  sudden  death  from  chloroform, 
and  few  and  happy  are  the  surgeons  who  have  never 
seen  it.     Here  we  must  place  those  cases  where  the 

12 


178  IMMEDIATE    AND    REMOTE 

patient  is  far  from  under,  perhaps  struggling  and 
shouting,  and  then  without  warning  draws  a  few 
deep  breaths  and  dies.  Here  also,  those  who  seem 
to  be  under,  but  whose  heart  and  respiration  cease  on 
being  lifted  into  position  for  the  surgeon.  Here, 
again,  those  who  have  been  given  a  mere  whiff  of 
the  anaesthetic  for  a  trifling  operation,  and  whose  life 
ebbs  away  at  the  bare  touch  of  the  knife. 

Until  recently,  it  was  supposed  that  these  fatalities 
were  due  to  sudden  reflex  stoppage  of  the  heart  by 
way  of  the  vagus,  and  that  view  was  given  in  our 
previous  editions.  Very  important  research  work  by 
Goodman  Levy  appears  to  demonstrate  that  the 
chloroform  acts  directly  on  the  ventricular  muscle, 
and  causes  it  to  fibrillate,  that  is,  to  enter  into 
flickering  irregular  contraction  of  individual  fibres, 
instead  of  performing  its  proper  rhythmical  systoles. 
Working  with  cats,  Levy  was  able  repeatedly  to 
observe  fatal  ventricular  fibrillation,  usually  heralded 
by  cardiac  irregularity,  and  always  when  the  chloro- 
form anaesthesia  was  light,  not  deep.  Stimulation 
of  sensory  nerves  under  a  light  anaesthesia  frequently 
caused  death  in  this  way  ;  in  other  cases,  the  animal 
recovered.  The  effect  was  just  the  same  if  both 
vagi  were  previously  cut.  Levy  found  great  diffi- 
culty in  discovering  exactly  by  what  means  the 
sensory  stimulus  affected  the  heart.  The  connection 
is  probably  complex.  If  the  chloroform  is  given  in  a 
perfectly  continuous  manner  without  intermissions, 
sudden  death — in  cats  at  any  rate — can  be  avoided. 
Struggling,  both  in  man  and  animals,  is  dangerous. 

An  apology  must  be  made  for  saying  again  what  we 


POISONING    BY    CHLOROFORM        179 

all  know,  yet  never  can  know  too  well.  It  is  courting 
disaster  to  hurry  the  patient  under.  We  must  feel 
the  pulse  all  the  time,  as  well  as  watch  the  pupil  and 
the  respirations.  "  Whiffs  "  are  far  more  dangerous 
than  proper  anaesthesia.  No  lifting,  or  cutting,  or 
painful  pressure  is  permissible  until  the  patient  is 
properly  under.  There  is  no  danger  of  an  overdose 
during  quiet  breathing  if  the  mask  is  kept  half  an 
inch  away  from  the  face.  If  Levy's  results  are  to  be 
accepted,  the  mask  must  not  be  entirely  withdrawn 
if  struggling  occurs,  but  every  effort  made  to  keep 
the  administration  constant. 

What  is  to  be  done  if  the  calamity  is  not  success- 
fully averted,  and  the  heart  and  breathing  cease  ? 
The  books  advise  a  dozen  expedients.  A  moment's 
consideration  of  physiological  principles  will  lead  us 
to  put  most  of  them  aside.  How  can  amyl  nitrite, 
which  is  simply  a  vasodilator,  possibly  help  a  heart 
that  is  fibrillating  ?  Strychnine  and  brandy  are 
perfectly  futile.  It  is  no  use  giving  oxygen  to  a 
patient  who  is  not  breathing.  "  Galvanization  of  the 
phrenics  "  is  equally  likely  to  galvanize  the  vagus. 

There  are  just  four  measures  which  matter.  The 
first  is  to  have  the  head  low,  so  as  to  keep  the  vital 
centres  alive.  The  second  is,  of  course,  artificial 
respiration,  which  fills  the  auricles  with  blood  as 
well  as  the  lungs  with  air,  averts  death  from  asphyxia, 
and  so  gives  the  heart  a  chance  to  recover  if  it  can. 
The  third  is  to  stimulate  the  heart  to  contract  again 
by  manual  compression,  if  possible  through  the 
diaphragm.  The  fourth  is  to  administer  as  quickly 
as  possible  atropine,  which  must  be  injected  right 


180  IMMEDIATE    AND    REMOTE 

into  the  heart  by  a  long  hypodermic  needle.*  Its 
value  in  overcoming  chloroform  inhibition  has 
been  abundantly  proved  by  Dixon  and  others  in 
dogs,  and  though  its  use  in  such  cases  in  man  is 
but  recent,  successes  are  already  recorded.  That 
there  have  been  failures  is  admitted,  but  there  is 
good  reason  to  hope  for  recovery  with  immediate 
injection  into  the  heart  itself.  There  is  ground  for 
hoping,  also,  that  a  preliminary  injection  of  scopola- 
mine, now  becoming  popular  for  employment  before 
the  administration  of  a  general  anaesthetic,  may 
help  to  eliminate  these  terribly  sad  occurrences. 

Several  patients  apparently  passed  beyond  the 
shadowy  Rubicon  which  separates  the  living  from 
the  dead  have  been  brought  back  to  life  by  rapidly 
opening  the  upper  abdomen  and  rhythmically 
squeezing  the  heart  against  the  chest  wall  through 
the  diaphragm. 

THE     FATAL    ADRENALIN-CHLOROFORM 
COMBINATION. 

In  Bristol,  it  has  been  well  recognized  for  seven 
or  eight  years  that  the  combination  of  chloroform 
anaesthesia  with  injections  of  adrenalin,  as  for 
instance  into  the  mucous  membrane  of  the  nose  to 
check  haemorrhage  in  a  nose  operation,  is  a  peculiarly 
deadly  association  of  remedies.  There  have  been 
several  fatalities,  and  a  number  of  narrow  escapes. 
Levy  has  done  most  valuable  service  in  working  out 

*  Atropine  solutions  are  apt  to  grow  a   mould  which  is   very 
poisonous.     If  such  a  growth  is  observed,  the  solution  must  no 
be  used. 


POISONING    BY    CHLOROFORM        181 

the  subject  upon  animals,  and  in  demonstrating 
that  adrenalin  has  a  peculiar  power  in  bringing  on 
the  ventricular  fibrillation  which  is  the  particular 
danger  of  a  light  chloroform  anaesthesia.  A  number 
of  deaths  have  now  been  recorded  from  this  cause 
in  medical  literature.  The  adrenalin-ether  combina- 
tion appears  to  be  safe. 

DELAYED    CHLOROFORM    POISONING. 

The  third  danger  is  subtle  and  unexpected  ;  it  has 
been  recognized  only  recently,  and  we  do  not  know 
how  to  treat  its  symptoms. 

In  Chapter  X.  reference  is  made  to  the  remark- 
able process  of  abnormal  decomposition  of  fats  which 
may  take  place  when  the  amount  of  glucose  supplied 
to  the  tissues  by  the  blood  is  deficient.  In 
these  circumstances,  /3-oxybutyric  acid,  diacetic  (or 
aceto-acetic)  acid,  and  acetone  are  produced,  and 
the  patient  is  poisoned  by  the  acids,  while  the  ace- 
tone imparts  a  sweet  odour  to  the  breath  and  urine. 
We  saw  that  starved  patients  and  diabetics  were 
particularly  liable  to  this  condition  of  "acidosis  "  or 
"  acetonaemia,"  as  it  is  variously  called.  Fat  chil- 
dren and  sufferers  from  peritonitis  are  frequently 
the  subjects  of  acidosis  after  operations  in  which 
chloroform  has  been  used,  and  there  is  greater  danger 
if  there  has  been  a  long  interval  between  the  last 
feed  and  the  anaesthetic.  A  prolonged  administration 
is  more  dangerous  than  a  brief  one.  The  train  of 
symptoms  is  referred  to  as  delayed  chloroform 
poisoning.  A  hospital  of  200  beds  may  perhaps 
furnish  one  or  two  such  cases  annually,  if  chloroform 


182  IMMEDIATE    AND    REMOTE 

is  used  frequently  as  the  anaesthetic  of  choice.  The 
signs  are  incessant  vomiting,  drowsiness  or  uncon- 
sciousness, and  a  sweet  acetone  odour  in  the  breath. 
Acetone  and  aceto-acetic  acid  are  present  in  con- 
siderable amount  in  the  urine.  A  trace  may  often 
be  found  after  any  anaesthetic.  Death  follows 
within  a  few  days.  At  the  post-mortem  examination 
the  liver,  kidneys,  and  other  organs  show  signs  of 
acute  fatty  degeneration.  Whether  this  is  the 
cause  or  the  consequence  of  the  acidosis  may  be  in 
doubt,  but  the  vomiting  and  drowsiness  are  almost 
certainly  due  to  the  effect  of  the  acid  intoxication 
on  the  brain.  Most  surgeons  who  are  aware  of  the 
condition  can  recall  sad  cases  where  an  operation 
promised  well,  but  this  fatal  complication  stepped 
in  and  banished  all  hope  of  a  favourable  issue. 
Recently  it  has  been  found  possible  to  imitate  the 
condition  in  experimental  animals.  To  draw  the 
practical  lesson,  we  can  at  present  hope  only  to 
prevent,  not  to  cure.  Every  patient  to  whom  it 
may  be  necessary  to  administer  chloroform  should 
be  guarded  as  far  as  possible  against  this  compli- 
cation. The  urine  should  be  tested  with  ferric 
chloride.  A  prolonged  starvation  should  be  avoided. 
Glucose  and  alkalies  have  been  advocated  as  remedies 
likely  to  prevent  trouble,  and  the  former  would 
appear  to  be  the  better.  If  possible,  ether  should  be 
given  to  patients  who  have  been  starved,  to  fat 
children,  and,  especially,  where  the  urine  strikes  a  red 
colour  with  ferric  chloride.  Diabetics  require  special 
care.  If  prolonged  vomiting  follows  recover}?  from 
the  anaesthetic,  the  poison  should  be  diluted  by  a 


POISONING    BY    CHLOROFORM        183 

large  injection  of  saline  into  the  rectum,  which  often 
works  wonders.  If  acetone  can  be  smelt  in  the 
breath,  glucose  or  alkalies,  or  both,  should  be  intro- 
duced into  the  blood  by  transfusion,  but  success  is 
not  very  probable,  as  these  remedies  cannot  restore 
the  fatty  liver  and  other  viscera  to  normal. 

Whether  the  acidosis  is  the  cause  of  the  vomiting, 
or  whether  the  starvation  consequent  on  the  vomiting 
causes  the  acidosis,  is  not  yet  certain,  but  we  may 
safely  attribute  the  drowsiness  to  the  acids  in  the 
blood,  and  they  probably  share  in  bringing  about 
the  fatal  termination. 

REFERENCES. 

Goodman  Levy. — Brit.  Med.  Jour.,  19 12,  ii,  p.  627. 
Goodman  Levy. — Heart,  19 13,  June,  p.  319. 


184 


CHAPTER   XII. 
NERVE    INJURIES. 

The  effects  of  nerve  section — Epicritic,  protopathic,  and  deep 
sensibility — Causation  of  trophic  lesions — Diagnosis  of  partial 
nerve  section — How  degenerated  nerve  is  regenerated — The 
results  of  primary  and  secondary  nerve  suture — Methods  of  dealing 
with  wide  gaps. 

IT  will  be  necessary  in  compressing  this  immense 
subject  into  the  limits  of  a  single  chapter  simply 
to  mention  the  better-known  phenomena,  and  refer 
to  the  original  monographs  those  who  wish  to  become 
more  fully  acquainted  with  the  interesting  results 
here  alluded  to. 

THE    EFFECTS    OF    DIVISION    OF    A    NERVE. 

The  effects  of  division  of  a  nerve  are  as  follows  : — 

(a).  Flaccid  paralysis  of  the  muscles  supplied,  with 
loss  of  reflexes. 

(b).  Loss  of  epicritic  sense  over  the  anatomical 
area  supplied  by  the  nerve.  Loss  ot  protopathic 
sense  over  an  area,  usually  smaller  and  encircled  by 
the  former.  Sometimes  loss  of  deep  sensibility  over 
an  area  smaller  still.  (These  terms  are  explained 
subsequently.) 

(c).  Reaction  of  degeneration. 

(d).  Wasting  of  muscles. 

(e).  Paralysis  of  the  pilomotor  nerves,  so  that  the 
hairs  lie  irregularly,  and  "  goose  skin  "  does  not  so 
readily  occur. 


NERVE    INJURIES  185 

(/).  Paralysis  of  sweating  in  the  area  supplied. 

(g).  Vascular  dilatation  (transitory). 

(h).  Trophic  changes,  such  as  glossy  skin,  onychia, 
sensitiveness  to  injury,  ulceration,  and  certain 
histological  changes. 

(*) .  Wallerian  degeneration  of  the  distal  part  of  the 
nerve  cut  off  from  its  nerve  cell. 

(/).  Nissl's  degeneration  (chromatolysis)  of  the 
nerve  cells  from  which  the  nerve  fibres  are  derived. 

Concerning  two  of  these  headings  a  few  words  of 
explanation  may  be  useful. 

The  terms  epicritic,  protopathic,  and  deep  sensibility 
were  introduced  by  Head  and  Sherren  to  denote 
some  very  important  distinctions,  failure  to  observe 
which  has  led  to  endless  mistakes  and  confusion  in 
the  past. 

We  may  take  as  an  illustration  the  consequences 
of  section  of  the  ulnar  nerve  at  the  elbow. 

Epicritic  Sense  will  be  lost  over  the  whole  of  the 
little  finger,  over  the  ulnar  half  of  the  ring  finger, 
and  over  a  corresponding  area  of  the  ulnar  surfaces 
and  border  of  the  hand,  both  back  and  front ;  that 
is  to  say,  over  the  region  described  in  the  anatomy 
books  as  supplied  by  this  nerve.  In  this  area  the 
patient  will  be  unable  : 

(i.)  To  detect  a  light  touch  ; 
(ii.)  To  detect  mild  ranges  of  heat  or  cold  ; 
(iii.)  To   distinguish   two   points  of   an   opened 

compass  as  separate  ;   and 
(iv.)  His  localization  will  be  imperfect. 
In  the  glans  penis  epicritic  sense  is  normally  absent. 

Protopathic  Sense  will  be  lost  over  the  whole  of 


186  NERVE    INJURIES 

the  little  finger,  and  over  a  small  area  of  the  ulnar 
border  of  the  hand.     In  this  region  the  patient  will 
be  unable  to  detect : 
(i.)  A  pin  prick  ; 
(ii.)  Extremes  of  heat  and  cold. 

Deep  Sensibility  will  be  lost  over  a  smaller  area 
still,  of  variable  dimensions.  That  is  to  say,  deep 
pressure  will  no  longer  be  appreciated  by  the  nerve 
endings  in  the  tendons,  joints,  and  bones. 

It  is  easy  to  deduce  from  the  above  that  serious 
pitfalls  await  the  unwary  observer  in  testing  such  a 
case.  He  may  make  pressure  on  the  little  finger  over 
the  metacarpo-phalangeal  joint,  or  over  the  ulnar 
border  of  the  ring  finger,  and  on  being  told  by  the 
patient  that  both  are  readily  felt,  may  conclude  quite 
incorrectly  that  the  ulnar  nerve  is  intact.  Testing 
with  a  pin  point  will  probably  bring  out  an  area  of 
anaesthesia  smaller  than  that  currently  supposed  to 
be  supplied  by  the  ulnar  nerve. 

The  only  reliable  method  of  testing  for  ancesthesia 
in  such  cases  is  to  make  the  patient  close  the  eyes,  and 
ask  him  to  indicate  with  a  finger  of  the  opposite 
hand  each  point  touched  as  lightly  as  possible  by  a 
pencil  of  wool.  In  testing  hairy  parts,  the  hairs 
should  be  shaved,  or  protopathic  or  deep  sensibility 
may  be  excited.  If  these  directions  are  followed,  an 
area  of  anaesthesia  will  be  mapped  out  corresponding 
to  the  anatomical  distribution  of  the  nerve. 

It  is  astonishing,  at  first  sight,  to  find  that  a 
patient  can  feel  a  pin-prick  or  pressure  in  a  region 
to  which  the  anatomist  can  trace  only  one  nerve, 
and  that  one  known  to  be  divided.     By  what  path 


NERVE    INJURIES  187 

is  he  made  aware  of  the  stimulus  ?  We  must  re- 
member that  tiny  nerve  twigs  are  to  be  found  in 
unexpected  places  ;  in  fasciae,  tendons,  and  bone, 
entering  them  far  up  the  limb  ;  in  the  walls  of 
cutaneous  vessels  ;  also  that  there  is  always  a  con- 
siderable overlap  of  the  distribution  of  neighbouring 
nerves,  at  any  rate  of  their  finest  terminals,  to  be 
followed  only  by  the  microscope.  The  deep  dis- 
tribution both  of  the  ulnar  and  radial  nerves,  in  the 
instance  given,  is  wider  than  their  cutaneous  dis- 
tribution. It  is  probable,  though  not  certain,  that 
extremes  of  temperature  and  painful  stimuli  are 
effective  because  they  penetrate  to  the  subepithelial 
tissues.* 

We  do  not  now  refer  the  so-called  "  trophic 
changes "  to  loss  of  innervation  by  special  nerve 
fibres  whose  sole  function  is  to  maintain  the  nutrition 
of  the  part.  The  vulnerability  of  the  parts  to  injury 
or  invasion  by  bacteria  can  be  accounted  for  without 
any  such  theory.  To  find  the  simpler  explanation, 
we  have  to  ask  how  a  particular  part  of  the  body  is 
able  to  obtain  a  better  blood-supply  at  need.  The 
answer  is  twofold.  There  is  a  local  chemical  action 
independent  of  nerves.  A  nerveless  limb  will  show 
hyperemia  when  a  mustard  plaster  is  applied.     A 


*  Head  denies  this,  believing  that  there  is  a  different  and  more 
primitive  sensory  apparatus,  the  protopathic,  detecting  extremes 
of  heat  and  cold,  and  a  more  recently  acquired  sensory  apparatus, 
the  epicritic,  detecting  the  smaller  ranges.  He  bases  his  opinion 
principally  on  the  examination  of  a  small  area  in  his  own  arm 
after  division  of  the  radial  nerve  :  in  this  area  epicritic  sense  was 
intact,  but  protopathic  sense  was  lost.  He  also  states  that  the 
viscera  possess  only  protopathic  sense  :  it  is,  however,  probable 
that  the  stomach  and  colon  have  no  temperature  sense  at  all. 


188  NERVE    INJURIES 

limb  all  but  amputated — left  connected  with  the 
body  only  by  its  main  artery  and  vein — will  show 
active  hyperaemia  if  its  blood-supply  has  been 
stopped  for  a  minute  and  then  released.  The 
chemical  substances  liberated  in  starved,  fatigued,  or 
damaged  tissues  exert  a  local  action  on  the  small 
arteries  supplying  them,  causing  them  to  dilate. 
But  there  is  also  a  vasomotor  reflex,  whereby  a  message 
is  sent  to  the  spinal  cord  and  vasomotor  centre  in 
the  medulla  asking  for  more  blood,  and  in  conse- 
quence vasodilator  impulses  are  sent  to  that  part, 
and  vasoconstrictor  impulses  to  the  rest  of  the  body. 
Normally,  these  occurrences  are  the  inevitable 
result  of  every  insult  or  injury,  of  every  invasion  by 
a  few  bacteria,  and  we  know  nothing  of  them  in 
consciousness.  But  when  the  nerves  of  the  part 
are  cut,  the  vasomotor  reflex  fails,  and  the  local 
hyperaemia  takes  place  too  late  to  check  the 
mischief. 

One  may  illustrate  the  circumstances  by  the 
analogy  of  a  guarded  frontier.  An  armed  raid  is 
made  by  an  enemy  ;  the  nearest  garrison  is  too 
weak  to  repel  it,  and  telegraphs  to  the  base  to  urge 
a  hasty  concentration  of  troops.  The  message  goes 
astray  because  the  wire  has  been  cut.  The  garrison 
must  make  what  resistance  they  can  with  the  aid  of 
local  volunteers  and  small  levies  summoned  by 
runners.  The  analogy  fails  in  this  particular,  that 
the  bacterial  invaders  of  the  human  frame  will  not 
remain  constant  in  numbers  till  the  belated  defending 
forces  are  at  last  mustered  against  them,  but  will 
multiply   a   thousand-fold   in   the   interval   and   do 


NERVE    INJURIES  189 

irreparable     damage.     This    is    the     pathology    of 
"  trophic  lesions/' 

We  pass  from  the  effects  of  total  nerve  section  to 
those  of  an  incomplete  division.  If  less  than  one- 
third  of  the  fibres  are  cut,  there  may  be  no  symptoms 
at  all  except  perhaps  pain.  In  general  the  sensory 
disturbance  is  greater  than  the  motor,  except  in 
such  a  nerve  as  the  musculospiral,  even  complete 
section  of  which  may  cause  no  anaesthesia.*  Epicritic 
sense  is  more  affected  than  protopathic.  If  any 
muscular  weakness  is  present,  a  very  characteristic 
electrical  reaction  may  be  obtained,  the  faradic 
response  being  lost,  but  the  galvanic  response  being 
brisk,  not  sluggish,  and  K.C.C.  greater  than  A.C.C. 
It  will  be  remembered  that  with  complete  division, 
the  galvanic  response  is  sluggish,  and  A.C.C.  is 
greater  than  K.C.C.  f  Pain  and  mottling  of  the 
skin  are  often  more  evident  with  partial  than  with 
complete  divisions  of  the  nerve. 

REGENERATION. 

Much  discussion  and  research  have  been  devoted 
in  the  past  decade  to  clearing  up  the  problem 
as  to  how  the  nerve  fibre  is  reproduced  when  it  has 
been  cut  off  from  its  nerve  cell  and  has  degenerated 
in  consequence.  We  know  that  the  fibres  peripheral 
to  the  section  degenerate  ;  we  also  know  that  if  the 
cut   ends   are   brought   together,    whether   at    once 


*  It  is  often  forgotten  that  the  radial  nerve  is  joined  in  the 
forearm  by  branches  of  the  musculocutaneous. 

1 1  do  not  explain  these  terms,  because  only  an  expert  would 
undertake  the  investigation  of-  the  electrical  reactions. 


190  NERVE    INJURIES 

(primary  suture)  or  many  months  later  (secondary 
suture),  medullated  nerve  will  in  time  be  repro- 
duced and  the  function  restored.  There  are  two 
schools  of  interpretation.  The  one  holds  that  the 
central  cut  end  buds  out  new  fibres  which  find 
their  way  down  the  old  track  to  their  old  destina- 
tions. This  is  the  theory  of  central  regeneration. 
The  other  school  contends  that  the  severed  piece 
of  nerve,  after  degenerating,  eventually  recovers 
itself,  and  the  continuity  of  its  fibres  is  restored, 
though  admittedly  very  few  of  them,  if  any,  acquire 
a  medullary  sheath.  It  only  needs,  according  to 
this  school,  that  the  nerve  thus  regenerated  should 
be  put  into  continuity  with  its  old  stump  for  its 
function  to  return  and  the  medullary  sheath  to 
develop.  This  is  the  theory  of  peripheral  regenera- 
tion. 

The  arguments  in  favour  of  the  latter  theory  were 
as  follows  : — 

(a) .  A  nerve  is  cut  across,  and  the  cut  ends  are  kept 
apart.  After  some  months,  it  is  said,  long  beaded 
fibres  may  be  demonstrated  by  suitable  staining 
methods,  running  continuously  the  whole  length  of 
the  nerve.  They  are  not,  in  ordinary,  surrounded  by 
a  medullary  sheath. 

It  is  objected  to  this  that  more  reliable  staining 
methods  show  only  the  discontinuous  fibres  which 
make  up  ordinary  white  fibrous  tissue  ;  and  that  no 
nerve  elements  are  present  at  all  in  the  degenerated 
piece  of  nerve  thus  cut  off  from  its  trophic  centre. 

(b).  It  has  been  claimed  repeatedly  that  if  in 
man  a  nerve  is  divided  and  not  sutured  for  manv 


NERVE    INJURIES  191 

months,  the  patient  may  have  some  degree  of 
recovery  of  sensation  in  the  anaesthetic  area  within 
a  few  days  after  the  belated  suturing.  We  know 
that  if  the  nerve  had  been  restored  by  primary  suture, 
it  would  have  been  months  before  any  recovery 
could  have  taken  place.  The  deduction  would  be 
that  the  isolated  segment  of  nerve  had  regenerated 
its  continuity,  and  only  needed  to  be  put  into  com- 
munication with  an  efficient  nerve  to  become  efficient 
itself. 

One  might  illustrate  the  two  theories  in  this  way. 
A  telegraph  wire  near  a  town  A  has  been  cut,  and 
the  whole  line  from  A  to  Z  completely  destroyed, 
leaving  only  the  track  of  the  broken  poles.  Villagers 
at  B,  C,  D,  etc.,  along  the  line  effect  a  certain  amount 
of  rough  repair,  and  finally  restore  a  continuous 
wire  from  B  to  Z.  After  some  months,  when  this 
has  been  done,  a  telegraph  operator  reunites  the 
wire  near  A.  Communication  with  Z  is  at  once 
restored.  This  illustrates  the  theory  of  peripheral 
regeneration. 

But  let  us  vary  the  process,  and  suppose  that  the 
operator  starts  from  A  and  unites  a  new  wire  to  the 
cut  end,  and  then  works  slowly  through  B,  C,  D, 
repairing  as  he  goes,  until  finally  he  reaches  Z. 
This  would  illustrate  the  theory  of  central  regenera- 
tion. If  it  be  true  that  communication  can  be 
restored  within  a  few  hours  of  the  reunion  of  the 
wires,  it  is  evident  that  peripheral  regeneration 
must  have  taken  place. 

It  is  doubtful,  however,  whether  the  clinical  obser- 
vations   of    immediate    return    of    sensation    after 


192  NERVE    INJURIES 

secondary  suture  are  trustworthy.  As  we  have  seen 
already,  there  are  many  fallacies  in  testing  sensation, 
and  since  these  have  been  recognized  there  is  no 
evidence  that  such  immediate  return  of  sensation 
has  been  proved  to  occur  in  any  well-authenticated 
case.  Patients  are  often  over-sanguine  as  to  the 
benefit  of  operations,  and  may  deceive  themselves. 
The  irritation  of  the  stamp  by  the  stitches  may 
induce  sensations  referred  to  the  surface.  It  is 
certain  that  in  most  cases  improvement  after  second- 
ary suture  is  not  more  but  less  rapid  than  after 
primary  suture. 

(c).  Bethe  and  others  have  found  that  if  a  nerve 
is  divided  and  not  sutured,  but  a  gap  is  left  which 
prevents  union,  after  a  year  or  two  a  few  medullated 
fibres  may  be  seen  in  the  degenerated  peripheral 
segment,  and  feeble  muscular  contractions  of  the 
paralysed  muscles  may  follow  stimulation.  He  took 
this  to  indicate  that  peripheral  regeneration  had 
occurred.  Langley  and  Anderson  have,  however, 
proved  that  these  few  medullated  fibres  are  derived 
from  some  other  nerve  in  the  limb,  which  has  grown 
down  the  old  path,  in  obedience  to  the  mysterious 
chemical  attraction  which  is  presumably  the  cause 
of  central  regeneration.  Thus  if  the  sciatic  nerve 
was  divided  and  the  upper  part  cut  away,  any 
medullated  fibres  found  in  the  tibial  nerves  will 
degenerate  after  section  of  the  anterior  crural  or 
obturator.  The  observation  thus  becomes  strong 
evidence  in  favour  of  the  theory  of  central  regener- 
ation. 

There  is  indeed  abundant  proof  in  favour  of  the 


NERVE    INJURIES  193 

view  that  the  new  nerve  fibres  formed  after  suture 
are  budded  out  from  the  cut  central  end.  It  will 
be  found  that  new  medullated  fibres  are  present  only 
in  the  proximal  part  of  the  regenerating  nerve  at 
first,  whereas  at  a  later  date  they  reach  the  periphery. 
Only  a  few  millimetres  may  have  regenerated  in  a 
month.  It  has  recently  been  shown,  by  Perroncito, 
that  the  fine  fibrils  which  constitute  the  axis  cylinders 
of  the  central  end  commence  to  grow,  curl,  bud,  and 
branch  within  a  few  hours  of  the  injury,  apparently 
"  feeling  for  "  the  old  track. 

Mott  and  Halliburton  have  shown  that  if  a  nerve 
is  cut  and  sutured,  and  time  allowed  for  regeneration, 
after  a  second  section  at  the  same  place  the  new 
medullated  fibres  peripheral  to  the  injury  all  degener- 
ate. Had  they  been  developed  in  situ  by  the  activity 
of  the  sheath  cells,  one  would  not  expect  degeneration 
after  the  second  section,  because  they  would  not  in 
that  case  have  been  cut  off  from  their  centre  of  origin. 
The  deduction  is  that  the  new  fibres  were  derived 
from  the  central  end. 

Convincing  proof  has  been  advanced  by  embry- 
ologists  that  the  nerves  in  the  embryo  are  not  formed 
in  situ,  but  are  budded  out  from  the  nervous  elements 
of  the  brain  and  spinal  cord.  By  removing  the 
medullary  groove  in  frog  embryos  and  planting  it 
in  lymph  clot,  Ross  Harrison  has  actually  observed 
the  developing  nerve  cell  grow  out  its  axon  at  the  rate 
of  20  /x  in  twenty-five  minutes.  The  outgrowing  axon 
is  actively  amoeboid.  He  was  able  also,  by  destroying 
the  ventral  part  of  the  developing  spinal  cord,  to 
obtain  tadpoles  in  which  the  muscles  had  no  motor 

13 


194  NERVE    INJURIES 

nerves.  If  it  is  allowed  that  in  the  embryo  the  nerves 
grow  out  from  the  central  nervous  system,  the  theory 
of  central  regeneration  is  placed  upon  a  strong  basis, 
and  indeed  it  is  now  almost  universally  accepted, 
whereas  fifteen  years  ago  it  was  losing  favour. 

Two  questions  of  great  interest  have  recently 
received  answers.  First,  Why  does  the  medullary 
sheath  of  a  nerve  fibre  break  up  into  fatty  droplets 
when  it  is  cut  off  from  its  trophic  centre,  that  is, 
from  its  cell  of  origin  in  the  central  nervous  system  ? 
Second,  How  does  the  budding  axis  cylinder  of  the 
central  end  of  a  divided  nerve  manage  to  find  its 
way  so  accurately  along  the  old  path  ? 

The  questions  are  intimately  related.  Each  fur- 
nishes the  answer  to  the  other.  The  medullary  sheath 
breaks  up  that  it  may  liberate  the  chemical  substance 
which  attracts  the  sprouting  axis  cylinder.  The  new 
fibre  follows  the  old  path,  because  of  the  chemical 
attraction  along  that  path. 

Nature  is  full  of  analogies  to  this  process  of  chemical 
attraction.  Chemical  particles,  though  infinitely 
diluted  with  air  or  soil,  attract  the  vulture  to  the 
corpse  in  the  desert,  or  the  bloodhound  to  the  hunted 
criminal.  Smell  is  only  a  chemical  analysis.  Simi- 
larly, the  leucocytes  crowd  out  of  the  vessels  to  an 
inflamed  area,  in  obedience  to  a  law  of  chemical 
attraction. 

If  two  celloidin  tubes  are  presented  to  the  central 
end  of  a  divided  nerve,  the  one  containing  emulsion 
of  liver,  and  the  other  emulsion  of  brain,  all  the 
sprouting  fibres  pass  into  the  brain  emulsion,  none 
into    the    tube    containing    liver  JForssman).     The 


NERVE    INJURIES  195 

disintegration  of  the  nervous  matter  lays  down  a  line 
of  bait  to  entice  the  regenerating  fibres  along  paths 
of  usefulness. 

The  phenomena  of  repair  after  suture  next  call 
for  remark.  It  may  be  said  at  once  that  the  sooner 
the  operation  is  performed  the  better  will  be  the 
results.  If  the  muscles  have  ceased  to  contract  to 
any  form  of  electrical  stimulus,  operation  is  useless. 
It  is  very  seldom  that  benefit  will  be  obtained  if 
two  years  have  elapsed  since  the  injury.  When 
secondary  suture  fails  to  give  a  good  result,  the 
fault  lies  not  with  the  degenerated  nerve  fibres  so 
much  as  with  the  nerve  cells  in  the  spinal  cord.  If 
asepsis  is  secured,  accurate  primary  suture  seldom 
if  ever  fails. 

Sherren  gives  average  time  relations  as  follows  : — 

5-25  weeks :  Commencing  return  of  protopathic 

sense. 
6-12  months  :  Complete  return  of  protopathic 

sense. 
12-18  months  :   Return  of  epicritic  sense. 
12-24  months  :    Motor  recovery. 

Taking  the  ulnar  nerve  as  an  example,  recovery 
may  be  hoped  for  in  twelve  months  when  it  has  been 
divided  at  the  wrist,  or  in  twenty-four  months  when 
the  injury  was  at  the  elbow. 

During  recovery,  a  remarkable  phenomenon  has 
been  described  by  Trotter,  who  had  nerve  sections 
performed  upon  himself.  Any  stimulus  over  the 
cutaneous  area  affected  gives  rise  to  a  decidedly 
painful  sensation,  referred  usually  to  the  most  distant 
part  of  that  area. 


196  NERVE    INJURIES 

Recovery  after  incomplete  division  of  a  nerve  is 
more  rapid,  usually  taking  less  than  six  months  for 
sensory  restoration  ;  it  is  perhaps  a  year  before 
motor  power  is  normal.  Protopathic  sense  does  not 
return  before  epicritic,  as  it  does  when  the  nerve  is 
completely  divided  ;  they  are  restored  side  by  side 
at  an  equal  rate. 

The  last  point  we  shall  consider  is  how  best  to 
proceed  when  so  much  nerve  has  been  lost  that  the 
ends  cannot  be  got  together.  Many  methods  have 
been  adopted,  some  of  which  are  of  little  or  no  value 
and  should  be  allowed  to  drop  out  of  use.  Amongst 
these  may  be  mentioned  the  introduction  of  a  bridge 
of  silk  or  catgut,  or  of  nerve  derived  from  a  cat,  dog, 
or  rabbit  (which  will  undergo  dissolution),  and  the 
device  of  splitting  the  nerve  longitudinally  and  turn- 
ing down  one-half  across  the  gap.  It  is  quite  evident 
why  these  fail.  The  silk,  catgut,  and  probably  the 
animal's  nerve,  cannot  provide  the  necessary  chemical 
attraction  for  the  down-growing  nerve  fibres.  The 
splitting  "  en-Y  "  does  not  lay  down  a  continuous 
"  scent  "  along  the  tract ;  it  is  broken  at  the  stem  of 
the  Y.  Infinitely  better  results  may  be  obtained  by 
suturing  into  the  interval  a  length  of  human  nerve. 
This  may  be  obtained  from  an  amputated  limb,  but 
it  is  always  possible  to  excise  several  inches  of  some 
unimportant  nerve  such  as  the  internal  cutaneous 
of  the  arm,  and  if  this  is  too  slender,  two  or  more 
pieces  may  be  used  parallel  to  one  another.  The 
nerve  can  be  located  before  the  anaesthetic  is  given 
by  testing  with  an  electric  current ;  when  the 
electrodes  are  applied  over  the  nerve  a  tingling  or 


NERVE    INJURIES  197 

pain  is  felt  throughout  its  distribution.  It  is 
an  advantage  to  protect  the  nerve  junctions  from 
invasion  by  fibrous  tissue  ;  this  may  be  done  by 
enclosing  them  in  a  ring  or  tube  of  superficial  vein, 
or  in  Cargile  membrane.  There  is  some  doubt  as  to 
whether  the  latter  does  any  good. 

There  is  yet  another  method,  which  is  sometimes 
the  only  one  available.  Langley  made  some  very 
interesting  experiments  on  the  effects  of  joining  up 
the  cut  ends  of  different  nerves,  and  found  that  their 
functions  could  be  transposed.  Thus  he  turned  the 
cat's  vagus  into  the  cervical  sympathetic,  and  allowed 
regeneration  to  take  place.  The  vagus  is  of  course 
the  nerve  of  swallowing,  and  therefore,  whenever 
the  cat  lapped  milk,  all  the  effects  of  stimulation  of 
the  cervical  sympathetic  were  seen  on  the  side 
operated  on — dilatation  of  the  pupil,  starting  of  the 
eye,  sweating,  retraction  of  the  nictitating  membrane, 
pallor  of  the  ear,  bristling  of  the  hair,  and  quicken- 
ing of  the  heart  beat.  When,  however,  the  (purely 
sensory)  lingual  nerve  and  the  (purely  motor)  hypo- 
glossal were  crossed  in  like  manner  there  was  no 
result. 

The  method  of  nerve  anastomosis  was  introduced 
into  practical  surgery  by  Ballance,  who  put  part  of 
the  spinal  accessory  nerve  into  the  peripheral  end 
of  the  degenerated  facial  nerve  to  relieve  intractable 
facial  palsy.  The  result  was  excellent,  but  there  was 
a  tendency  of  course  for  the  face  and  the  trapezius 
to  contract  together,  and  smiling  was  accompanied 
by  jerking  of  the  shoulder.  To  avoid  this  the  hypo- 
glossal is  now  utilized  instead  of  the  spinal  acces- 


198  NERVE    INJURIES 

sory.  It  was  hoped  that  there  was  a  wide  field  of 
usefulness  before  this  device  of  nerve  anastomosis, 
especially  in  infantile  palsy.  For  instance,  if  the 
anterior  tibial  muscles  and  peronei  alone  were 
affected,  the  external  popliteal  might  be  divided  and 
the  peripheral  end  put  into  a  notch  in  the  internal 
popliteal.  Unhappily,  published  results  are  very 
disappointing,  at  any  rate  in  the  case  of  infantile 
paralysis ;  probably  even  the  anterior  horn  cells 
supplying  useful  muscles  have  been  somewhat 
damaged,  and  cannot  take  on  more  than  ordinary 
work.*  The  method  remains  hopeful,  however,  for 
paralysis  following  other  forms  of  nerve  disease  or 
injury. 

REFERENCES. 
A  few  recent  papers  of  importance  are  : — 

Ballance  and  Stewart. — "  The  Healing  of  Nerves," 
London,  1901. 

Head,  Sherren,  and  Rivers. — Brain,  1905,  pp.  99,  116. 

Harrison,  Ross. — "  Embryonic  Transplantation  and  De- 
velopment of  the  Nervous  System,"  Anatom.  Record, 
Bait.,  1908,  ii,  No.  9.  "  Observations  on  the  Living 
Developing  Nerve  Fibre,"  Amer.  Jour,  of  Anatomy, 
1907,  vii. 

Kilvington  and  Osborne. — Jour,  of  Physiol.,  1909,  vol. 
xxxviii,  pp.  268,  276. 

Langley  and  Anderson. — Jour,  of  Physiol.,  vol.  xxxi, 
1904,  pp.  365,  418. 

Mott  and  Halliburton. — Proc.  Roy.  Soc.  B.,    1906,  lxxviii, 

p.  259. 
Mott. — "  Present  Position  of  the  Neurone  Doctrine."    Pres. 
Address,  Pathological  Section,  Med.  Chir.  Soc,  London, 

1909. 
Sherren. — "  Injuries    of     Nerves,  and    their    Treatment," 

London,   1908. 
Bethe. — "  Allgemeine  Anatomie  und  Physiologie  des  Nerven- 

systems,"  Leipsig,  1903. 

*  See  Murray  and  Warrington,  Lancet,  1910,  i,  p.  912. 


199 


CHAPTER    XIII. 

THE    SURGICAL    PHYSIOLOGY    OF   THE 
SPINAL    CORD. 

The  effects  of  division  of  the  posterior  nerve  roots — The  diagnosis 
and  localization  of  tumours  of  the  spinal  cord — The  exact  diagnosis 
of  injuries  of  the  spinal  cord. 

THE    EFFECTS    OF    DIVISION    OF    THE 
POSTERIOR    NERVE    ROOTS. 

THE  effects  may  be  classified  as  follows  : — 
i.  Anaesthesia  of  the  spinal  area  of  skin 
supplied.  The  distribution  of  these  in  the  human 
subject  has  been  worked  out  thoroughly,  and  the 
charts  of  Head,  Sherrington,  and  others  are  well 
known.  Section  of  a  single  nerve  root  scarcely  ever 
causes  any  complete  loss  of  sensation. 

2.  Ataxia  of  the  corresponding  limb,  which  may  be 
severe. 

3.  Loss  of  tone,  leading  to  marked  flaccidity  of 
the  corresponding  limb. 

4.  A  variable  degree  of  functional  paralysis. 
Owing  to  the  loss  of  sensory  impulses,  the  ataxia, 
and  lack  of  tone,  the  patient,  man  or  animal,  prefers 
not  to  use  the  limb,  although  there  is  not  a  genuine 
paralysis. 

5.  Loss  of  reflexes. 

6.  Trophic  lesions,  such  as  ulcers,  whitlows,  etc. 

7.  Usually  not  shock.     This  is  rather  surprising. 


200         THE    SURGICAL    PHYSIOLOGY 

I  have  taken  the  blood-pressure  in  two  patients 
whilst  four  or  five  nerve-roots  in  the  lumbar  and 
sacral  plexus  were  cut  on  each  side,  and  there  has 
been  no  sudden  fall.  There  was  a  steady  drop 
throughout  the  whole  operation  (under  open  ether 
anaesthesia)  amounting  to  less  than  eight  millimetres 
of  mercury. 

8.  Certain  degenerative  changes.  The  posterior 
columns  of  the  spinal  cord  show  Wallerian  degenera- 
tion running  up  to  their  termination  in  the  gracile 
and  cuneate  nuclei  of  the  medulla.  As  Warrington 
has  pointed  out,  in  animals  the  cells  of  the  anterior 
horn  on  the  same  level  as  the  severed  roots  show 
signs  of  chromatolysis,  or  dissipation  of  their  Nissl 
granules.  I  have  recently  been  able  to  demonstrate 
this  in  man.  A  patient  who  had  been  treated 
for  gastric  crises  by  resection  of  the  posterior  nerve 
roots  from  the  seventh  to  the  tenth  dorsal,  died  about 
two  months  afterwards.  In  the  cervical  region  all 
the  nerve-cells  were  normal,  but  in  the  region  of  the 
divided  roots  more  than  half  the  anterior  horn  cells, 
and  all  the  cells  of  Clark's  column,  showed  marked 
chromatolysis.  This  is  interesting  in  the  light  of 
the  various  affections  of  the  motor  functions  just 
mentioned. 

The  surgery  of  the  posterior  nerve  roots  is  yet  in 
its  infancy,  but  it  promises  to  have  a  future.  When 
it  is  resorted  to  earlier,  it  will  most  probably  have  a 
greater  value. 

There  are  two  main  indications  for  dividing  the 
posterior  nerve  roots.  The  one  is  pain,  and  the  other 
extreme  rigidity,  in  the  course  of  spastic  paraplegia 


OF    THE    SPINAL    CORD  201 

or  hemiplegia.  The  pain  may  be  due  to  such  a 
cause  as  the  crises  of  locomotor  ataxia,  or  the  agonies 
of  inoperable  cancer.  It  is  more  successful  for  the 
latter  than  for  the  former. 

When  many  roots  are  cut  for  spasticity,  it  is 
necessary  to  leave  one  or  two  intact,  or  a  very 
decided  amount  of  ataxy  may  be  induced.  The 
relief  of  adductor  or  other  spasm  is  often  very 
marked,  if  it  has  not  become  permanent  in  con- 
sequence of  fibrous  shortening  of  the  muscles  and 
tendons. 

THE     DIAGNOSIS     AND     LOCALIZATION     OF 
TUMOURS    OF    THE    SPINAL    CORD. 

Tumours  of  the  spinal  cord  do  not  occur  so 
commonly  as  tumours  of  the  brain,  but  the  results  of 
surgical  removal  are  a  good  deal  better.  It  becomes 
important,  therefore,  to  know  how  to  make  the 
diagnosis. 

Before  entering  upon  this  subject,  we  must  remind 
ourselves  of  the  functions  of  the  great  paths  or  tracts 
running  up  or  down  the  spinal  cord. 

Descending  Tracts. — The  pyramidal  tracts  convey 
motor  impulses  from  the  cortex,  and  particularly 
those  acquired  movements  which  call  for  skill  and 
finesse.  They  also  inhibit  muscular  tone.  The 
rubrospinal  tract  (Monakow's  bundle)  controls  stock 
movements  such  as  standing,  sitting,  and  walking. 
This  tract  starts  in  the  red  nucleus  in  the  isthmus, 
and  it  is  largely  by  its  means  that  a  man  whose 
pyramidals  have  been  destroyed  in  the  brain  may 
still  be  able  to  get  about.     It  would  appear,  also, 


202         THE    SURGICAL    PHYSIOLOGY 

that  this  tract  carries  down  impulses  that  inhibit 
any  excess  of  muscular  tone.  The  vestibulospinal 
and  other  tracts  pass  down  in  the  an tero -lateral 
columns,  from  the  region  of  the  pons  and  medulla. 
They  are  important  paths  for  motor  impulses,  at 
any  rate  in  animals ;  in  monkeys  a  section  of  these 
tracts  produces  more  paralysis  than  one  involving 
the  crossed  pyramidal.  They  appear  to  convey 
impulses  increasing  muscular  tone,  so  that  when  the 
pyramidal  fibres  are  damaged,  as  by  a  haemorrhage 
in  the  internal  capsule,  muscular  tone  is  increased 
and  a  spastic  hemiplegia  results.  There  are,  however, 
other  descending  paths  open  to  this  class  of  impulses, 
some  of  them  crossing  in  the  cord. 

Ascending  Tracts. — The  dorsal  cerebellar  tract 
passes  from  the  cells  of  Clarke's  column  of  the  same 
side  to  the  cerebellum.  It  conveys  sensations 
derived  from  muscles,  joints,  and  tendons  to  the 
cerebellum,  and  so  keeps  it  informed  of  the  posi- 
tion of  every  joint  and  the  state  of  contraction  of 
every  muscle. 

The  ventral  cerebellar  tract  of  Gowers  is  composite 
in  nature.  Most  of  the  fibres  are  crossed.  Some  pass 
to  the  cerebellum,  others  to  the  mid-brain,  and  the 
important  spinothalamic  tract  conveys  sensations 
of  heat,  cold,  and  pain,  and  probably  also  tactile 
sense,  to  the  brain. 

The  posterior  columns  (of  Goll  and  Burdach)  are 
also  uncrossed  in  the  spinal  cord,  and  convey  tactile 
sense,  muscular  sense,  joint  sense,  and  so-called 
"  tactile  discrimination,"  by  which  we  determine 
whether  two  compass  points  are  single  or  double  ; 


OF    THE    SPINAL    CORD  203 

the  sense  (stereognosis)  by  which  we  recognize  unseen 
objects  by  the  feel — as  on  putting  a  hand  into  a 
pocket  containing  coins,  keys,  a  penknife,  paper, 
etc. — also  travels  by  this  route. 

Thus  we  find  that  whilst  muscular  sense,  stereo- 
gnosis and  tactile  discrimination  pass  up  the  cord 
uncrossed,  heat,  cold,  and  pain  sense  cross,  usually 
about  six  segments  above  their  point  of  entry,  and 
there  is  a  cell-station  in  the  grey  matter.  Hence 
syringomyelia  and  other  lesions  of  the  grey  matter 
abolish  temperature  and  pain  sense.  Sherrington 
has  shown  that  the  pain  impulses  are  not  totally 
crossed  ;  a  few  pass  up  on  the  same  side.  Tactile 
sense,  apparently,  can  follow  either  of  these  two 
routes. 

A  tumour  of  the  spinal  cord  : — 

i.  May  affect  the  nerve-roots,  in  which  case  the 
symptoms  may  be  confined  to  those  roots. 

2.  May  press  on  one  side  of  the  spinal  cord.  In 
this  case  there  is  usually  pain  radiating  along  the 
nerve-roots  involved  at  the  same  time,  which  is 
important  in  the  diagnosis. 

Let  us  take  the  case  of  a  tumour  in  the  left  lower 
cervical  area.     This  will  involve  : — 

(i).  The  emerging  roots  of  the  lower  cervical  nerves 
on  the  left  side,  causing  pain,  dulling  of  sensation, 
and  flaccid  paralysis  with  loss  of  reflexes,  wasting, 
and  reaction  of  degeneration,  in  the  left  arm. 

(ii).  The  pyramidal,  rubrospinal,  and  vestibulo- 
spinal tracts  on  the  left  side,  causing  paralysis  of 
the  left  leg.  Inasmuch  as  the  pyramidal  and  rubro- 
spinal tracts  are  involved,   muscular  tone  will  be 


204        THE    SURGICAL    PHYSIOLOGY 

greatly  increased ;  the  impulses  leading  to  this 
increase  perhaps  descend  on  the  other  side  of  the 
cord.  There  will  be,  therefore,  rigidity  of  the  left 
leg  and  exaggerated  reflexes. 

(iii).  The  cerebellar  tracts  and  posterior  columns  of 
the  left  side,  causing  loss  of  muscle  and  joint  sense, 
and  loss  of  tactile  discrimination  and  recognition  of 
objects  on  the  left  side. 

(iv).  The  spinothalamic  tract,  by  which  heat,  cold, 
and  pain  travel  up  from  the  right  leg,  will  also  be 
pressed  upon. 

Tactile  sense  may  not  be  lost  in  either  leg,  as  a 
double  path,  the  one  crossed  and  the  other  uncrossed, 
is  open  to  it. 

Table  to  Illustrate  the  Effects  of  a  Tumour 
of  the  Left  Lower  Cervical  Region. 


Right  Arm. 
Normal. 


Left  Arm. 

Pain.  Some  anaesthesia. 
Flaccid  paralysis,  loss  of 
reflexes,  wasting. 


Right  Leg. 

Loss  of  sense  of  heat, 
cold,  pain. 


Left  Leg. 

Loss  of  muscular  sense, 
joint  sense,  tactile  discri- 
mination and  recognition  of 
objects.  Spastic  paralysis ; 
exaggerated  reflexes. 


3.  It  may  arise  in  the  central  grey  matter.  In  this 
case  there  will  be  loss  of  the  heat,  cold,  and  pain 
senses  on  both  sides,  but  tactile  and  muscular  sense 
will  remain.     There  may  be  some  spastic  paralysis 


OF    THE    SPINAL    CORD  205 

of  both  legs.  In  the  early  stages  the  diagnosis  from 
syringomyelia  may  be  only  a  matter  of  opinion. 

4.  In  some  cases  it  may  produce  bilateral  spastic 
paralysis  with  involvement  of  the  sphincter  func- 
tions and  with  anaesthesia  without  any  dissociation 
phenomena.     The  diagnosis  is  then  very  difficult. 

Each  of  the  thirty-one  nerve-roots  issuing  from 
the  spinal  cord  has  a  definite  distribution,  which  may 
be  motor,  sensory,  and  visceral,  and  these  have  now 
been  ascertained  with  some  accuracy  by  a  combina- 
tion of  anatomical,  physiological,  and  clinical 
methods.  As  given  in  the  various  textbooks  and 
monographs,  the  information  is  a  good  deal  more 
than  most  of  us  can  carry  conveniently  in  our 
memories.  It  is  hoped  that  the  bare  elements  set 
down  in  the  table  may  be  found  easier  to  remember, 
and  adequate  for  most  purposes.  No  two  accounts 
agree  exactly. 

The  main  points  may  be  emphasized  first.  With 
regard  to  the  sensory  distribution,  there  is  a  good 
deal  of  overlap,  especially  in  the  hand,  where  the 
seventh  cervical  supplies  the  radial  half,  the  eighth 
cervical  the  inner  half,  and  the  first  dorsal  the  one 
and  a  half  fingers  to  which  the  ulnar  nerve  may  be 
traced.  The  twelve  dorsal  nerves  supply  the  chest 
and  abdomen  in  bands  like  successive  strips  of 
plaster  stretched  round  the  body ;  the  nipple  lies 
between  the  fourth  and  fifth  dorsal,  and  the  umbilicus 
between  the  ninth  and  tenth.  If  we  place  the  open 
hand  on  the  thigh  just  below  and  parallel  to  Poupart's 
ligament,  we  cover  the  first  lumbar  area  ;  the  next 
handbreadth  below  is  the  second  lumbar,  and  the 


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208        THE    SURGICAL    PHYSIOLOGY 

next,  including  the  region  of  the  patella,  is  the  third 
lumbar.  The  small  sciatic  nerve  area  corresponds  to 
the  second  sacral,  and  the  internal  saphenous  nerve 
area  to  the  fourth  lumbar  segment. 

With  regard  to  motor  distribution,  the  fifth  cervical 
supplies  the  deltoid -f- biceps -f  supinator  longus  group, 
as  well  as  the  dorsal  scapular  muscles  and  rhomboids. 
In  infantile  palsy  and  other  anterior  horn  or  nerve- 
root  affections,  these  muscles  may  be  found  paralysed 
and  atrophied  in  company.  On  the  other  hand,  a 
fracture  of  the  spine  irritating  this  segment  brings 
about  a  characteristic  position  of  the  arms  *Y  .  The 
first  dorsal  gives  off  sympathetic  branches  dilating 
the  pupil. 

The  anatomy  of  the  lumbo-sacral  plexus  makes  it 
easy  to  remember  that  the  quadriceps  and  adductors 
must  be  supplied  from  the  lumbar  nerves,  whereas  the 
hamstrings  and  crural  muscles  are  innervated  from  the 
sciatic  roots.  There  is  a  general  tendency  for  flexors 
to  derive  their  nerve  supply  from  a  level  slightly 
below  that  for  the  extensors.  It  is  easy  to  see 
why  this  should  be  the  case  if  we  glance  at  a 
quadruped,  where  the  flexors  are  posterior  to  the 
extensors. 

Flaccid  paralysis  and  anaesthesia  of  the  lower  limbs, 
with  sphincter  trouble,  may  be  due  to  a  tumour 
growing  either  in  the  cauda  equina  or  in  the  conus 
medullaris  of  the  cord  itself.  The  diagnosis  is  often 
difficult,  but  tumours  of  the  cauda  are  usually 
characterized  by  a  slower  course,  asymmetry,  very 
violent  pain,  and  Lasegne's  sign — pain  on  flexing  the 
thigh  and  thus  pulling  on  the  nerve-roots.     Operative 


OF    THE     SPINAL    CORD  209 

interference  gives  better  results  in  these  cases  than 
in  those  where  the  cord  itself  is  affected. 

In  a  few  cases  recently  recorded,  where  section  of 
posterior  nerve  roots  had  failed  to  relieve  pain,  a 
surgeon  has  divided  the  pain-path  in  the  antero- 
lateral region  of  the  cord.  To  give  success,  this 
should  be  done  on  both  sides,  although  by  far  the 
greater  number  of  pain-fibres  are  crossed.  Sherrington 
worked  out  the  path  by  dividing  the  mesencephalon 
in  dogs,  after  which  injury  they  still  turn  and  try  to 
bite  and  growl  if  a  foot  is  hurt,  although  they  cannot, 
of  course,  psychically  feel  it.  If  then  the  spinal  cord  is 
hemisected  on  the  right  side,  painful  stimuli  applied 
to  the  right  foot  produce  much  livelier  snapping  and 
growling  than  the  same  on  the  left  side. 

THE    EXACT    DIAGNOSIS    OF    INJURIES    OF   THE 
SPINAL    CORD. 

The  following  lesions  of  the  cord  may  be  responsible 
for  symptoms  of  paralysis  or  anaesthesia  after  an 
injury  to  the  back. 

i.  Simple  concussion,  the  injuries  being  micro- 
scopical or  functional  only,  and  the  paralysis  transient. 

2.  Complete  division  of  all  the  nervous  elements. 

3.  Pressure  on  the  cord  due  to  bone,  callus,  or  a 
foreign  body  not  causing  s.  total  transection. 

4.  Haemorrhage  into  the  spinal  membranes. 

5.  Haemorrhage  into  the  cord  itself. 

6.  Later  complications  such  as  myelitis,  traumatic 
neurasthenia,  etc. 

This  is  not  the  place  to  consider  all  these  in  their 

14 


210        THE    SURGICAL    PHYSIOLOGY 

surgical  bearing.  We  want  to  look  at  them  in 
relation  to  the  physiology  of  the  spinal  cord. 

Both  in  man  and  in  animals,  and  particularly  in 
monkeys,  a  transverse  injury  to  the  cord  leads  to 
the  phenomenon  known  as  spinal  shock.  All  the 
reflex  functions  are  severely  depressed,  and  there  is 
transient  paralysis  and  anaesthesia.  Sherrington  has 
shown  in  animals  that  a  transection,  e.g.,  in  the 
upper  dorsal  region,  causes  spinal  shock  only  distal 
to  the  lesion  ;  the  cervical  cord  is  normal.  If  after 
recovery  has  occurred  a  second  section  is  made  in 
the  mid-dorsal  region,  no  spinal  shock  is  produced. 
Evidently  it  was  due  to  the  withdrawal  of  impulses 
running  downwards  from  the  brain-stem,  probably 
from  the  region  of  Deiter's  nucleus,  because  tran- 
section of  the  upper  pons  or  mesencephalon  does  not 
cause  spinal  shock. 

A  total  transection  of  the  cord  in  man,  not  in 
animals,  affects  profoundly  the  functions  of  the 
segments  below  the  injury,  and  either  from  the  first 
or  after  the  lapse  of  a  little  time  they  lose  their  reflex 
functions,  the  bladder  and  rectum  and  their  sphincters 
become  paralysed,  and  the  effect  is  much  the  same 
as  it  would  have  been  if  the  isolated  portion  of  the 
cord  had  been  removed  in  toto.  In  animals,  the 
reflex  functions  persist. 

Considerable  difficulty  may  be  experienced  for  a 
day  or  two  in  deciding  whether  a  patient  is  suffering 
from  a  complete  division  of  the  cord  due  to  the  nip 
at  the  moment  of  fracturing  the  spine,  or  whether 
the  symptoms  are  due  merely  to  concussion.  In 
the  latter  case  a  few  days'  rest  will  effect  a  cure. 


OF    THE    SPINAL    CORD  211 

Sometimes  one  can  get  a  hint  earlier.  If  the  distri- 
bution of  the  paralysis  does  not  correspond  to 
the  distribution  of  the  anaesthesia,  and  if  the  sym- 
ptoms are  asymmetrical,  it  is  probable  that  they  are 
due  partly  at  least  to  concussion.  In  either  case  it 
is  very  seldom  that  any  useful  purpose  will  be  served 
by  operating,  unless  the  injury  involves  the  cervical 
region  or  the  cauda  equina. 

When  the  cord  is  involved,  but  has  not  suffered 
a  functional  transection,  the  paralysis  will  probably 
be  spastic  in  nature,  and  operation  is  more  hopeful 
because  there  may  be  something  exercising  injurious 
pressure  which  can  be  removed. 

Haemorrhage  into  the  spinal  membranes  produces 
pain  and  spasm  by  involving  the  issuing  nerve  roots. 
In  addition,  there  will  probably  be  some  evidence  of 
pressure  on  the  cord,  producing  spastic  paralysis  and 
some  anaesthesia  below  the  lesion. 

Haemorrhage  into  the  centre  of  the  cord  sometimes 
abolishes  the  pain  and  temperature  senses  while 
tactile  sense  escapes.  There  will  probably  be  spastic 
paraplegia  as  well. 

It  will  not  be  necessary  to  refer  here  to  the  diagnosis 
of  the  later  complications,  such  as  myelitis  and  the 
various  neuroses. 

Unfortunately  the  central  nervous  system  is  so 
highly  specialized  that  it  has  lost  the  power  of 
regeneration  after  injury,  not  only  in  man  (unless  we 
accept  the  evidence  of  the  famous  Stewart-Harte  case !) 
but  also  in  nearly  all  animals.  The  newt,  it  is  true, 
can  form  a  new  cord  if  its  tail  is  lopped  off,  but  the 
newt  has  marvellous  powers  of  regeneration,  and  can 


212      PHYSIOLOGY    OF    SPINAL    CORD 

even  grow  a  new  lens  if  the  front  of  its  eye  is  removed ! 
Histological  evidence  of  partial  regeneration  has 
been  obtained  in  mammals  by  Marinesco  and  others, 
but  not  functional  restoration. 

REFERENCES. 

Forster. — Zeitschrift  f.  orthopdd  Chir.,  1908,  Bd.  xxii,  p.  203. 
Head  and  Thompson. — "  The  Grouping  of  Afferent  Impulses 

in  the  Spinal  Cord,"  Brain,  1906,  p.  537. 
A.    Rendle    Short. — Proc.    Royal   Soc.    Medicine,    Surgical 

Section,  July,  191 1. 
Sherrington. — "  Integrative  Action  of  the  Nervous  System." 


•213 


CHAPTER    XIV. 
CEREBRAL    LOCALIZATION. 

The  causation  and  significance  of  optic  neuritis — Localization 
in  the  cerebellum — Tumours  in  the  cerebellopontine  angle. 
Localization  of  sensation  in  the  cerebral  cortex — Functions  of 
the  frontal  cortex — Spasticity — Apraxia — Aphasia — Misleading 
localizing  signs  of  cerebral  tumour — The  cerebrospinal  fluid. 

IT  will  be  necessary  here  to  assume  that  the  reader 
has  an  ordinary  acquaintance  with  the  structure 
and  functions  of  the  brain.  We  shall  confine  our- 
selves to  a  brief  reference  to  the  most  important 
advances  of  the  past  decade  in  providing  evidence 
for  the  localization  of  tumours,  abscesses,  and 
traumatic  lesions,  and  therefore  for  their  successful 
treatment  by  operation. 

OPTIC     NEURITIS. 

It  has  long  been  in  doubt  why  optic  neuritis  should 
develop  in  cases  of  cerebral  tumour.  It  has  been 
attributed  to  the  effects  of  chronic  meningitis,  and 
to  over-filling  of  the  third  ventricle,  with  consequent 
pressure  on  the  underlying  optic  chiasma.  It  is 
now  definitely  established  by  the  experiments  of 
Cushing  and  Bordley,  and  confirmed  by  clinical 
experience,  that  it  is  a  pressure  effect.  The  growth 
of  the  neoplasm  causes  a  great  and  continued  rise 
of  intracranial  pressure  ;  this  tends  to  dam  back 
the  lymph  flow  returning  in  the  sheath  of  the  optic 


214  CEREBRAL    LOCALIZATION 

nerve.  The  usual  consequence  of  lymphatic  obstruc- 
tion is  produced,  namely,  ©edematous  swelling  of  the 
area  drained.  So  the  optic  cup  fills  up,  the  disc  is 
obscured  by  transudate,  and  the  vessels  are  buried 
from  view  in  the  oedema  fluid.  All  this  may  be 
exactly  reproduced  by  intracranial  pressure  in  dogs, 
and  when  the  pressure  is  removed,  restitution  to 
normal  takes  place. 

Several  methods  of  raising  the  intracranial  pressure 
were  employed,  the  best  results  being  obtained  by 
the  insertion  of  sponge-tent  material  inside  the 
skull.  Swelling  and  oedema  of  the  disc,  tortuosity 
of  the  veins,  and  over-distention  of  the  lymph- 
sheath  around  the  optic  nerve  were  all  marked. 
Relief  of  the  pressure  rapidly  cured  them. 

Although  we  use  the  conventional  term  "  neuritis," 
the  histological  changes  are  not  those  of  inflammation. 
For  instance,  there  is  no  arterial  hyperaemia,  and 
the  principal  infiltration  is  with  cells  of  connective 
tissue  origin,  not  leucocytes. 

Further,  it  has  been  stated  by  many  observers, 
and  recently  defended,  with  all  his  great  authority 
and  experience,  by  Sir  Victor  Horsley,  that  the  degree 
of  the  neuritis  in  the  two  eyes  is  a  most  reliable 
guide  as  to  the  side  of  the  tumour.  It  is  not  so  much 
the  amount  of  swelling  that  is  to  be  taken  into 
account  as  the  age  and  extent  of  the  changes.  These 
nearly  always  commence  at  the  upper  nasal  quadrant 
of  the  disc.  Thus,  optic  neuritis  best  marked  in  the 
right  eye  is  of  great  value  in  pointing  to  a  right-sided 
tumour.  The  further  forward  the  tumour,  the  more 
constant  does  this  rule  become. 


CEREBRAL    LOCALIZATION  215 

It  is  well  known  that  even  if  a  cerebral  tumour 
cannot  be  localized,  palliative  trephining  should  be 
performed  to  relieve  headache  and  save  the  sight. 
If  this  is  undertaken  early,  the  optic  neuritis  passes 
off.  As  the  tentorium  transmits  pressure  badly, 
the  trephining  should  be  in  the  temporal  region  for 
supratentorial  tumours,  and  in  the  occipital  region 
for  cerebellar  tumours. 

Another  valuable  observation  which  we  owe  to 
Cushing  is  that  raised  intracranial  pressure,  par- 
ticularly by  cerebral  tumour,  induces  a  considerable 
limitation  of  the  field  of  vision  for  blue  ;  indeed, 
there  may  be  actual  blue-blindness. 

THE    CEREBELLUM. 

We  have  been  in  urgent  need  of  some  improvement 
in  our  means  of  localizing  tumours  and  abscesses 
in  the  cerebellum.  During  the  past  ten  years,  at  the 
Bristol  Royal  Infirmary  there  have  been  eight  cases 
of  temporo-sphenoidal  abscess,  all  of  which  have 
been  successfully  diagnosed,  and  ten  cases  of  cere- 
bellar abscess,  of  which  only  three  were  correctly 
located  ;  in  three  of  these  ten  cases  the  cerebrum 
was  explored  in  vain,  and  in  two  the  lateral  sinus 
was  thought  to  be  the  cause  of  the  symptoms.  It 
remains  to  be  seen  how  far  the  fresh  light  recently 
thrown  on  the  subject  and  herein  set  forth  will 
help  us  to  obtain  materially  better  results. 

Sir  Victor  Horsley  and  R.  H.  Clarke  have  recently 
revised  our  knowledge  of  the  functions  and  relation- 
ships of  the  cerebellum  by  an  ingenious  method. 
Reconstructions  of  a  monkey's  head  have  been  made 


216  CEREBRAL    LOCALIZATION 

by  cutting  frozen  sections  and  then  piecing  them 
together  again  ;  by  this  means  it  was  possible  to 
build  a  frame  of  metal  to  fit  about  the  head  of  a 
living  monkey,  carrying  an  insulated  needle  which 
could  be  thrust,  through  a  small  trephine  hole,  into 
any  desired  portion  of  the  cerebellum,  its  cortex, 
or  its  deep  nuclei  (roof  nuclei),  the  exact  position  of 
the  point  of  the  needle  having  been  determined  by 
a  study  of  the  head  reconstructed  from  the  frozen 
sections.  By  this  means  various  parts  could  be 
stimulated  electrically  without  doing  any  but  the 
slightest  damage  to  the  overlying  structures  ;  more- 
over, by  passing  in  a  strong  current  and  using  a 
double  needle  shielded  nearly  to  the  points,  small 
electrolytic  lesions  either  of  the  cortex  or  of  the 
roof  nucleus  could  be  made,  and  the  resulting 
degenerations  studied  by  suitable  staining  some 
weeks  afterwards. 

The  general  result  was  to  prove  that  the  cortex 
cerebelli  is  a  receiving  platform,  and  that  its  axons 
merely  pass  to  the  roof  nuclei,  from  which  the  efferent 
tracts  start.  Stimulation  of  the  cerebellar  cortex  by 
ordinary  currents  produces  no  obvious  response  ; 
stimulation  of  the  roof  nuclei  causes  movements  of 
the  eyes  and  sometimes  of  the  limbs.  We  see  here 
the  reason  why  laterally  situated  tumours  or  abscesses 
lie  so  quiet. 

The  classic  signs  of  a  lesion  of  the  cerebellum, 
determined  both  by  physiologists  and  by  clinicians, 
are  the  following  :  —  (i)  Ataxia  ;  (2)  Atonia  ; 
(3)  Asthenia  ;  (4)  Tremor  :  these  all  affect  the  same 
side  as  the  lesion  ;    (5)  Nystagmus  ;    (6)  Vertigo. 


CEREBRAL    LOCALIZATION  217 

i.  Ataxia. — This,  one  of  the  most  constant  signs, 
is  easily  detected  if  the  patient  is  able  to  walk. 
When  he  is  in  bed,  it  may  be  brought  out  by  making 
hirn  try  to  pronate  and  supinate  rapidly  for  a  minute 
or  two  ;  or  to  make  and  unmake  a  fist  quickly,  over 
and  over  again.  This  sign  is  the  more  convincing 
if  it  is  unilateral. 

2.  Atonia  is  very  variable  ;  the  knee-jerks  may 
be  absent,  normal,  or  excessive,  and  may  change 
day  by  day. 

Thiele  and  others  have  proved  that  the  great 
increase  of  tone  noticed  in  man  or  animals  after 
lesions  involving  the  pyramidal  and  other  long 
descending  tracts  depends  on  the  integrity  of  Deiter's 
nucleus.  This  lies  just  at  the  junction  of  the  pons 
and  medulla,  beneath  the  outer  part  of  the  floor  of 
the  fourth  ventricle,  and  therefore  in  close  relation 
to  the  cerebellum.  If  it  is  destroyed,  or  if  it  is  cut 
off  from  influencing  the  spinal  cord  by  a  complete 
transverse  division  below  Deiter's  nucleus,  the 
spasticity  and  increased  reflexes  which  ordinarily 
follow  lesions  of  the  motor  paths  will  fail  to  develop. 

Some  cerebellar  abscesses  and  tumours  press  on 
the  pyramids  (above  their  decussation)  but  not  on 
Deiter's  nucleus.  These  cause  increase  of  tone  on 
the  opposite  side.  Others  destroy  Deiter's  nucleus, 
and  cause  loss  of  tone  on  the  same  side.  Others  do 
not  involve  either,  and  tone  may  be  normal,  or  a 
little  increased  on  the  same  side  as  the  lesion. 

3.  Asthenia  may  be  evidenced  by  weakening  of  the 
grip,  tendency  to  fall,  or  drooping  of  the  head  on  the 
affected  side.     It  is  not  very  constant. 


218  CEREBRAL    LOCALIZATION 

4.  Tremor  is  only  occasionally  in  evidence. 

5.  Nystagmus. — These  curious  jerkings  of  the  eyes 
are  of  considerable  importance  in  the  diagnosis  of 
cerebellar  affections,  because,  although  seen  in  such 
conditions  as  disseminated  sclerosis,  they  are  very 
unusual  with  localized  intracranial  tumours.  Un- 
fortunately they  are  not  constantly  present  even 
when  the  lesion  is  in  the  cerebellum,  and,  on  the 
other  hand,  are  usually  to  be  observed  in  patients 
with  disease  of  the  labyrinth  (vestibule  and  semi- 
circular canals) .  Seeing  that  most  cases  of  cerebellar 
abscess  follow  otitis  media,  it  has  been  very  difficult 
to  be  certain,  in  the  past,  whether  any  nystagmus 
in  a  patient  with  a  suppurating  ear  was  due  to  the 
labyrinth,  or  the  cerebellum,  or  both. 

Barany,  of  Vienna,  has  shown  that  it  is  possible 
to  induce  nystagmus  in  a  normal  person  by  stimulat- 
ing the  labyrinth.  This  may  be  done  either  by 
rotating  the  patient,  or  by  allowing  hot  or  cold  (not 
tepid)  water  to  trickle  in  as  far  as  the  membrana 
tympani.  Hot  water  in  the  right  ear  causes  a 
nystagmus  in  which  the  eyes  slowly  turn  to  the  left 
and  are  corrected  by  rapid  jerkings  to  the  right  ; 
with  cold  water  the  rapid  jerkings  would  be  to  the 
left. 

If  a  patient  with  a  suppurating  ear  has  nystagmus, 
and  it  is  desired  to  know  whether  this  is  due  to 
affection  of  the  labyrinth  or  of  the  cerebellum,  hot 
or  cold  water  should  be  injected  to  see  if  the  nystagmus 
can  be  reversed  in  direction.  If  it  can,  the  labyrinth 
cannot  be  at  fault ;   it  must  be  the  cerebellum. 

Again,  a  patient  with  severe  vertigo  following  on 


CEREBRAL    LOCALIZATION  219 

otitis  media  may  be  suffering  from  labyrinthitis  or 
from  cerebellar  abscess.  If  injection  causes  no 
nystagmus,  the  labyrinth  is  destroyed. 

TUMOURS    IN    THE    CEREBELLO-PONTINE 
ANGLE. 

This  is  a  very  common  location  for  cerebellar 
tumours,  and  a  comparatively  favourable  one  for 
surgery,  seeing  that  in  many  instances  the  growth 
is  simple,  and  can  be  enucleated  without  recurrence. 
Allen  Starr  finds  in  the  literature  sixty-nine  cases 
cured  by  removal.  In  many  of  these  there  was 
restoration  to  good,  in  some  to  perfect,  health. 
Diagnosis,  therefore,  becomes  peculiarly  important. 

In  addition  to  the  signs  mentioned  above,  certain 
nerve-root  symptoms  may  develop,  and  the  pons  may 
be  pressed  on.     Mental  trouble  is  quite  unusual. 

We  may  classify  the  evidence  as  follows  : — 

1.  General :  headache,  vomiting,  optic  neuritis, 
slow  pulse,  blue-blindness,  perhaps  convulsions. 

2.  Cerebellar  signs :  staggering,  vertigo,  ataxia, 
weakness,  tremor,  and  perhaps  absent  knee-jerk ; 
these  may  be  unilateral,  on  the  same  side  as  the 
growth.     Nystagmus. 

3.  Nerve-root  symptoms  affecting  the  same  side  : 
pressure  on  the  fifth,  with  corneal  anaesthesia  and 
loss  of  reflex,  and  weakness  of  jaw  muscles  ;  pressure 
on  the  sixth,  with  internal  strabismus  ;  pressure  on 
the  seventh,  with  facial  weakness  ;  pressure  on  the 
eighth,  with  tinnitus,  loss  of  perception  for  upper 
notes  (tested  by  Galton's  whistle),  or  absolute  deaf- 
ness ;    pressure  on  the  ninth,  tenth,  and  eleventh, 


220  CEREBRAL    LOCALIZATION 

with  dysphagia,  laryngeal  palsy,  cardiac  attacks, 
etc.  ;  pressure  on  the  twelfth,  with  deviation  of 
the  protruded  tongue.  Of  these,  the  facial  and 
auditory  nerves  are  most  often  affected,  there  being 
complete  unilateral  deafness  in  most  of  the  cases. 
In  cerebellar  tumours  these  two  nerves  may  be 
interfered  with,  but  not  to  any  considerable  degree. 
4.  Pressure  on  the  pons,  causing  crossed  hemiplegic 
weakness,  with  exaggerated  reflexes  and  extensor 
response.  The  cases  may  live  for  years,  but  there 
is  a  liability  to  sudden  death  by  crowding  of  the 
cerebellum  down  through  the  foramen  magnum. 

LOCALIZATION  OF  SENSATION  IN  THE 
CEREBRAL  CORTEX. 

Hearing. — Although  it  is  certain  that  monkeys 
which  have  suffered  bilateral  removal  of  the  temporal 
cortex  give  every  evidence  that  they  can  hear,  it  is 
very  difficult  to  be  equally  certain  that  sounds  are 
still  appreciated  in  consciousness  by  them,  and 
recognized  for  what  they  signify.  It  is  no  more 
evidence  of  conscious  hearing  that  a  monkey  looks 
round  when  a  bell  sounds,  than  it  is  of  conscious  pain 
that  a  man  with  a  fractured  spine  withdraws  a  foot 
pricked  by  a  pin. 

At  any  rate,  there  is  a  fair  amount  of  evidence, 
both  anatomical  and  clinical,  to  locate  this  function 
in  the  temporal  region,  and  none  to  locate  it  else- 
where. The  most  convincing  observation  on  record 
was  made  by  Cushing,  who  stimulated  the  exposed 
temporal  cortex  in  a  conscious  man,  and  the  patient 
said  that  he  noticed  a  buzzing  noise. 


CEREBRAL    LOCALIZATION  221 

Vision. — There  is  abundant  evidence  that  visual 
sensations  are  received  on  the  mesial  surfaces  of  the 
occipital  lobes,  just  above  and  just  below  the 
calcarine  fissure.  Histologically,  the  area  is  mapped 
out  by  the  white  line  of  Gennari ;  it  barely  encroaches 
posteriorly  on  the  convexity  of  the  hemisphere. 

The  left  half  of  each  retina  is  represented  in  the 
left  cerebral  cortex,  and  the  right  half  of  each  retina 
in  the  right  cortex.  The  fovea  centralis  of  each  eye 
has  a  bilateral  representation.  The  upper  half  of  each 
retina  is  projected  above  the  calcarine  fissure  ;  the 
lower  half  of  each  retina  below  the  fissure.  Therefore 
a  tumour  of  the  left  cortex  above  the  calcarine 
fissure  would  render  the  upper  left  quadrant  of  each 
eye  psychically  blind,  and  the  patient  would  be 
unable  to  see  objects  downwards  and  to  his  right. 

A  smaller  lesion,  however,  does  not  produce  a 
smaller  patch  of  blindness  ;  it  merely  reduces  the 
visual  acuity  over  the  whole  of  the  corresponding 
quadrant. 

Cutaneous  Sensation. — It  is  universally  agreed 
that  the  main  receiving  platform  for  cutaneous  sensa- 
tion is  situated  in  the  postcentral  (ascending  parietal) 
gyrus,  just  behind  the  fissure  of  Rolando,  and  that  the 
general  arrangement  is  the  same  as  that  of  the  motor 
centres  ;  thus,  the  sensory  centre  for  the  leg  is  nearest 
the  vertex,  opposite  the  origin  of  the  pyramidal  fibres 
for  the  leg  ;  next  come  the  arm  centres,  and  lowest 
of  all  those  for  the  face  and  head. 

The  localization  in  the  limbic  lobe  once  advocated 
by  Schafer  and  others  following  him,  has  now  been 
given  up,  even  by  its  author.     Doubt  still  remains, 


222  CEREBRAL    LOCALIZATION 

however,  whether  the  precentral  or  motor  cortex 
takes  any  share  in  appreciating  cutaneous  sensation. 
If  so,  it  is  quite  secondary  to  the  part  played  by  the 
postcentral  convolution. 

It  is  very  difficult  to  be  sure  to  what  extent 
animals  feel  after  the  removal  of  small  parts  of 
either  the  postcentral  or  precentral  convolutions, 
and  very  diverse  views  have  been  expressed  ;  it  is 
quite  certain  that  a  small  lesion  does  not  induce  com- 
plete anaesthesia.  It  is  probably  wiser  to  put  faith 
principally  in  the  human  evidence  on  such  a  subject. 
It  is  abundantly  proved  that  lesions  involving  the 
ascending  parietal  convolution  almost  always  cause 
a  certain  degree  of  interference  with  sensation,  never 
amounting  to  a  complete  hemiansesthesia,  which, 
indeed,  occurs  only  in  hysteria,  or  very  transitorily 
after  an  apoplectic  stroke.  Bergmark  quotes  thirty- 
three  cases  of  lesions  of  this  gyrus  with  sensory 
symptoms  but  no  paralysis. 

Cushing  excited  the  postcentral  convolution  in 
two  conscious  patients  who  had  previously  been 
trephined,  by  unipolar  faradic  stimulation.  He 
found  that  the  brain  itself  was  devoid  of  any  sort 
of  feeling,  but  that  sensations  of  stroking,  tingling, 
or  warmth  were  produced,  referred  to  the  hand  of 
the  opposite  side.  The  sensation  was  quite  well 
defined  and  localized  ;  one  area  corresponded  to  the 
index  finger,  and  another  to  the  back  of  the  hand. 
When  the  electrode  was  applied  in  front  of  the  fissure 
of  Rolando  instead  of  behind,  the  fingers  or  hand 
moved,  but  there  was  no  sensation.  An  incision  in 
the  postcentral  convolution  was  quite  painless,  and 


CEREBRAL    LOCALIZATION  223 

caused  some  numbness  of  all  forms  of  sensation  in 
the  hand. 

It  is  more  difficult  to  be  certain  whether  the 
ascending  frontal  or  motor  convolution  has  also  any 
sensory  function  ;  if  so,  it  is  less  obvious  than  in 
the  case  of  the  postcentral  convolution.  Naturally 
occurring  lesions  limited  to  the  front  of  the  fissure  of 
Rolando,  and  carefully  studied  before  and  after  death, 
are  rare,  and  the  evidence  is  conflicting ;  some 
showed  paralysis  but  no  sensory  loss,  whereas  others 
had  both  motor  and  sensory  impairment.  Many 
years  ago,  before  it  was  realized  that  the  convolutions 
in  front  of  and  behind  the  fissure  of  Rolando  differed 
in  function,  Ransom  and  also  Laycock  observed  that 
a  tingling  sensation  was  elicited  when  they  stimulated 
the  exposed  cortex  in  a  conscious  man,  and  apparently 
they  both  applied  the  electrodes  in  front  of  the 
fissure  ;  Cushing  and  others  have  failed  to  confirm 
this.  Recently  Sir  Victor  Horsley  has  published  an 
account  of  the  only  case  in  which  he  has  removed  a 
cortical  centre  (part  of  the  hand  area)  without 
encroaching  upon  the  ascending  parietal  gyrus  (for 
athetosis).  Immediately  after  the  operation  there 
was  complete  flaccid  paralysis  of  the  arm  and  some 
interference  with  sensation.  The  hand  could  detect 
cold,  but  not  warmth,  stroking  with  a  wool  pencil  was 
not  felt  on  the  ungual  phalanges,  there  were  inaccuracy 
of  location  of  pain  and  touch  and  loss  of  the  sense  of 
position,  and  objects  placed  in  the  hand  were  not 
recognized  by  touch  (astereognosis).  A  year  later, 
movement  was  recovered,  except  for  some  spastic 
paralysis  in  the  two  ulnar  fingers  ;    there  were  still 


224  CEREBRAL    LOCALIZATION 

astereognosis,  inaccuracy  of  location,  and  slight 
dulling  of  sensation  over  the  ulnar  border  of  the 
hand.  If  the  lesion  had  involved  the  postcentral 
convolution,  the  sensory  symptoms,  in  his  experience, 
would  have  been  much  more  marked.  The  athetosis 
was  cured. 

Interference  with  sensation  is  of  course  no  \)rooi 
that  a  cerebral  tumour  is  in  the  cortex  ;  it  may  be 
found  with  a  lesion  of  the  optic  thalamus,  internal 
capsule,  isthmus,  pons,  or  medulla.  In  twenty-six 
cases  of  hemiplegia  due  to  some  trouble  in  the  internal 
capsule,  Bergmark  found  evidence  of  sensory  im- 
pairment in  all  who  were  intelligent  enough  to  be 
tested  with  accuracy  by  modern  methods,  although 
there  was  never  complete  hemianaesthesia  to  all  forms 
of  stimuli. 

The  relations  of  the  cerebral  cortex,  optic  thalamus, 
and  mid-brain  to  various  forms  of  sensation  have 
recently  been  made  the  subject  of  an  interesting 
research  by  Head  and  Gordon  Holmes.  The  special 
character  of  interference  with  sensation  in  lesions  of 
the  cortex  in  the  Rolandic  area  is  the  untrustworthi- 
ness  of  the  response.  The  stimulus  will  be  felt  at  one 
time  but  not  at  another  ;  the  sensation  may  persist 
after  the  stimulus  is  withdrawn,  hallucinations  may 
be  present,  and  local  fatigue,  affecting  sensation  in 
the  paralysed  limb  but  not  in  the  other,  is  easily 
induced.  All  forms  of  sensation,  heat,  cold,  tactile, 
localization,  stereognosis,  and  weight  sense,  may  be 
diminished,  muscular  sense  (sense  of  passive  move- 
ments and  of  posture)  being  particularly  liable  to 
reduction. 


CEREBRAL    LOCALIZATION  225 

It  is  the  special  function  of  the  optic  thalamus, 
or  rather  of  its  mesial  nuclei,  to  impart  emotional 
tone,  pain  or  pleasure,  to  the  sensation.  These  are 
thalamic,  not  cortical,  in  their  appeal  to  conscious- 
ness. Fibres  from  all  parts  of  the  cortex  converge 
on  the  lateral  nucleus  of  the  optic  thalamus,  and  tend 
to  control  and  inhibit  excessive  pain  or  pleasure 
arising  from  the  impulses  received  from  the  spinal 
cord.  When  this  lateral  nucleus  is  destroyed,  and 
only  the  mesial  part  of  the  thalamus  left  intact, 
stimuli  are  much  more  painful  or  (in  the  case,  for 
instance,  of  stroking  or  of  warmth)  more  pleasurable 
than  on  the  normal  side.  Sometimes  music  produces 
a  remarkable  emotional  effect  in  the  affected  limbs, 
especially  if  it  is  solemn  or  majestic. 

There  are  of  course  other  signs  of  involvement  of 
the  optic  thalamus,  such  as  hemianaesthesia,  athetosis, 
and  transient  hemiplegia. 

FUNCTIONS  OF  THE  FRONTAL  CORTEX. 

It  is  well  known  that  the  great  motor  centres  are 
limited  to  the  ascending  frontal  or  precentral  con- 
volution. This  has  been  abundantly  proved  [by 
many  methods  :  by  the  study  of  paralysis  following 
localized  lesions  in  man,  or  removals  in  man  or 
apes  ;  by  electrical  stimulation  in  man  and  apes  ; 
and  histologically,  by  the  limitation  to  this  region 
of  the  giant  pyramidal  or  Betz  cells,  which  are  the 
only  cells  to  undergo  chromatolysis  when  the  pyra- 
midal tracts  are  destroyed  in  the  spinal  cord. 

It  often  becomes  of  great  importance  to  the  surgeon 
to  know  whether  a  tumour  causing  hemiplegia  is 

15 


226  CEREBRAL    LOCALIZATION 

accessible,  either  in  the  cortex  or  close  beneath  it, 
or  inaccessible,  in  the  internal  capsule  or  isthmus. 
The  principal  evidences  of  the  former  are  the  occur- 
rence of  monoplegias,  the  face,  arm,  or  leg -being 
affected  alone  without  the  others,  whereas  lesions  of 
the  internal  capsule  would  paralyse  all  three  ;* 
secondly,  persistent  aphasia  may  be  present ;  and 
thirdly,  there  may  be  recurring  convulsions.  The 
degree  of  sensory  impairment  is  not  of  much  assist- 
ance, but  the  considerations  just  advanced  may 
sometimes  be  helpful. 

There  is  a  good  deal  of  evidence  that  if  the  paralysis 
is  of  a  flaccid  typi  the  lesion  is  most  probably 
cortical,  though  Kie  converse  is  not  necessarily  true. 
Thiele  has  demonstrated  in  animals  that  tone  is 
increased  by  impulses  from  Deiters'  nucleus  in  the 
medulla,  and  inhibited  by  impulses  generated  in  the 
optic  thalamus  and  conducted  by  the  rubrospinal 
tract  (Monakow's  bundle).  It  is  this  tract  which 
subserves  the  stock  movements  such  as  standing  and 
walking,  which  can  often  be  carried  out  after  complete 
destruction  of  the  pyramidal  tract.  In  man,  a 
cortical  lesion  is  often  (not  always)  accompanied  by 
a  flaccid  paralysis  with  no  Babinski  sign  and  with 
normal  or  diminished  reflexes  (see  cases  quoted  by 
Bergmark),  but  when  the  optic  thalamus  and  internal 
capsule  are  involved,  there  is  always  marked  rigidity. 
Pressure  on  the  isthmus,   pons,  medulla,   or  spinal 


*  In  monkeys  the  fibres  to  the  head,  arm,  and  leg  are  grouped 
in  bundles  in  the  internal  capsule,  but  apparently  this  is  not  the 
case  in  man,  and  consequently  small  lesions  cause  mild  hemiplegia, 
not  monoplf-gia. 


CEREBRAL    LOCALIZATION  227 

cord  will  probably  damage  the  rubrospinal  tract  as 
well  as  the  adjacent  pyramidal  tracts,  and  so  set 
up  spasticity,  unless  the  whole  cord  is  functionally 
divided,  in  which  case  impulses  descending  from 
Deiters'  nucleus  (possibly  in  the  vestibulospinal  tract), 
are  also  cut  off,  and  a  flaccid  paralysis  results. 

It  is,  however,  true  that  irritation  of  the  cortex, 
such  as  may  be  present  just  after  a  traumatic  lesion, 
or  during  the  growth  of  a  tumour,  may  cause  early 
contracture,  so  we  should  regard  the  presence  of 
rigidity  as  an  equivocal  sign,  but  absence  of  rigidity 
as  evidence  of  a  cortical  lesion. 

The  frontal  cortex  lying  in  front  of  the  motor  region 
is  described  as  a  "  silent  area,"  and  extensive 
tumours,  degenerations,  or  injury  may  produce  few 
or  no  symptoms.  In  a  case  under  the  writer's  care,  a 
wound  one  inch  deep  into  the  brain,  from  the  vertex 
to  the  nose,  caused  by  a  chopper,  made  absolutely 
no  difference  to  the  woman's  character,  capacity, 
or  intelligence,  and  indeed  produced  no  symptoms 
at  all  beyond  concussion,  although  she  was  under 
observation  for  many  months.  In  the  famous 
American  crowbar  case,  where  a  large  part  of  the 
frontal  cortex  on  both  sides  was  destroyed,  there  was 
no  paralysis,  but  on  returning  to  work  the  man, 
previously  a  capable  foreman,  had  become  weak, 
vacillating,  inattentive,  and  profane.  There  are 
quite  commonly  signs  of  mental  dullness  in  patients 
with  frontal  lesions.  In  cats  there  are,  after  excisions 
of  the  frontal  cortex,  changes  in  the  disposition, 
and  recently  acquired  tricks  may  be  lost. 


228  CEREBRAL    LOCALIZATION 

According  to  Sir  Victor  Horsley,  abscesses  of  the 
brain  involving  the  Rolandic  area  usually  lead  to  a 
raised  temperature  on  the  opposite  side  of  the  body, 
whereas,  if  the  location  is  in  front  of  or  behind  this 
region,  the  temperature  is  subnormal. 

APRAXIA. 

More  definite  evidence,  however,  is  now  available. 
There  are  a  number  of  carefully  studied  cases  on 
record  in  which,  with  no  actual  paralysis,  there  has 
been  a  remarkable  clumsiness  in  the  performance  of 
movements  requiring  any  skill,  and  in  which  the 
patient  has  been  quite  unable  to  make  some  movement 
voluntarily  or  in  response  to  command,  although  he 
may  unconsciously  do  that  very  thing  under  the 
influence  of  emotion  or  by  accident.  This  condition 
is  called  apraxia.  It  is  most  convincing  when  it  is 
unilateral.  Thus,  a  musician  may  lose  the  power  of 
playing  his  instrument,  or  the  clerk  his  power  of 
writing.  In  Liepmann's  classic  case,  one  of  the  first 
to  be  described,  there  was  apraxia  of  the  right  arm 
and  leg.  "  Asked  to  put  his  right  forefinger  on  his 
nose,  he  said,  '  Yes/  and  with  his  stretched  forefinger 
executed  wide  circling  movements  in  the  air.  He 
made  the  correct  movement  at  once  with  his  left 
hand.  Asked  to  close  his  right  hand  into  a  fist, 
he  performed  various  absurd  movements  of  his  arm 
and  body,  but  attained  the  required  goal  at  once  with 
his  left  hand.  When  asked  to  give  the  examiner 
a  certain  object  with  his  right  hand,  he  frequently 
picked  up  the  wrong  thing,  and  still  holding  it  in 
his  hand,  used  the  left  to  take  up  the  required  object 


CEREBRAL    LOCALIZATION  229 

and  present  it  to  the  physician."  A  patient  of  de 
Buck's,  asked  to  lift  her  right  arm,  crossed  it  over 
her  body,  put  it  in  her  left  axilla,  and  after  making 
various  other  vigorous  but  futile  efforts,  said  plain- 
tively, "  Je  comprends  bien  ce  que  vous  voulez, 
mais  je  ne  parviens  pas  a  le  faire  "  :  this  just  expresses 
the  condition. 

In  some  of  the  cases,  there  is  imperfect  recognition 
of  objects  or  of  their  uses  (agnosia),  but  these  are 
complicated  and  cannot  be  described  here. 

It  is  an  important  fact  that  apraxia  of  the  left 
arm  is  common  in  right  hemiplegics,  whereas  apraxia 
of  the  right  arm  rarely  occurs  in  left  hemiplegics ; 
moreover,  in  the  cases  where  there  are  apraxia  of  the 
left  side  and  hemiplegia  of  the  right,  there  is  evidence 
that  the  lesion  is  cortical,  not  in  the  internal  capsule. 
Thus  Liepmann  examined  eighty-three  hemiplegic 
patients,  with  these  results  : — 

Forty-two  had  left  hemiplegia  ;  they  could  nearly 
all  obey  directions  with  the  right  arm. 

Forty-one  had  right  hemiplegia  ;  of  these  20  had 
apraxia  of  the  left  arm,  and  14  in  this  group  also 
had  aphasia  (therefore  the  lesion  was  cortical)  ;  21 
had  no  apraxia,  and  of  these  only  4  had  aphasia  (in 
most  of  the  other  17  cases  the  lesion  was  probably  in 
the  internal  capsule). 

Of  course,  as  left-handed  persons  form  one- 
twentieth  of  the  community,  it  is  possible  to  find  a 
few  cases  of  left  hemiplegia  with  right  apraxia. 

There  is  good  ground,  then,  for  believing  that  the 
centres  which  consciously  initiate  voluntary  move- 
ments for  both  sides  of  the  body  are  limited  to  the 


230  CEREBRAL    LOCALIZATION 

left  cortex  in  right-handed  people,  and  that  the 
precentral  convolutions  are  merely  the  departure 
platforms  for  messages  from  the  brain  to  the  cord. 
Instructions  are  sent  to  the  right  precentral  convolu- 
tion by  way  of  the  corpus  callosum.  It  is  still  in 
doubt  whether  the  above-mentioned  initiating  centre 
is  in  the  left  precentral  gyrus,  or  whether  it  lies  in 
front  of  this,  in  the  first  and  second  frontal  convolu- 
tions, as  most  neurologists  maintain.  It  is  quite 
certain  that  a  lesion  of  the  front  part  of  the  corpus 
callosum  is  characterized  by  apraxia  of  the  left  arm ; 
this  important  discovery  may  well  lead  to  successful 
surgical  removal  of  tumours  there  situated.  A  lesion 
in  the  left  frontal  cortex  may  cause  apraxia  of  both 
arms  ;  there  will  probably  be  right  hemiplegia*  as 
well,  which  would  mask  the  condition  in  the  right  arm. 
To  sum  up,  a  lesion  is  cortical  if  there  are  present : — 

i.  A  monoplegia. 

2.  Hemiplegia  with  either  (i)  Aphasia  which 
persists ;  (ii)  Recurring  convulsions ;  (iii)  Flac- 
eidity  ;    (iv)  Apraxia  of  the  opposite  side. 

Left-sided  apraxia  without  hemiplegia  indicates  a 
lesion  of  the  corpus  callosum. 

APHASIA. 

The  various  types  of  aphasia  have  always  presented 
problems  of  great  complexity  but  of  much  interest. 
Recent  studies  of  the  subject  have  been  very  revolu- 
tionary in  their  tendency.  We  used  to  learn  that 
there  were  three  main  centres  for  the  appreciation 
and  utterance  of  language,  namely  : — 


CEREBRAL    LOCALIZATION 


231 


1.  The  motor  centre,  controlling  utterance,  in 
Broca's  convolution  (the  third  left  frontal). 

2.  The  auditory  word  centre,  appreciating  spoken 
language,  in  the  posterior  part  of  the  second  left 
temporal  convolution.  This  was  also  regarded  as 
dominating  and  being  necessary  for  the  activity  of 
the  other  two  centres. 

3.  The  visual  word  centre,  appreciating  written 
language,  in  the  left  angular  gyrus,  behind  and  above 
the  auditory  word  centre. 

Recently,  however,  the  searching  analyses  of  Marie 
and  his  pupils  have  raised  very  grave  doubts  about 
the  first  and  third  of  the  above,  and  many  neuro- 
logists have  agreed  that  Broca's  convolution  has  no 
speech  function  at  all ;  very  few  now  defend  the 
existence  of  a  separate  visual  word  centre. 

Briefly,  the  contention  of  Marie  and  Moutier  may 
be  put  thus.  Between  1861  and  1906,  there  have 
been  published  304  cases  of  aphasia  with  autopsy. 
Of  these  201  were  useless  and  103  were  relevant. 


Useless 


Relevant 


(Lesion  too  extensive         -         -         -    175 
(Badly  described        -         -         -         -     26  201 
^Favourable  to    /Cortical  lesions  with 
Broca's  local-     J      aphasia  -         -       8 

1  Subcortical    lesions 
(     with  aphasia  -     11      19 

/Aphasia,  but  Broca's 

convolution  normal  57 
No  aphasia,  but 
h  Broca's  convolu- 
tion destroyed  (in 
two  cases,  bilateral 
destruction)  -         -     27     84 


ization 


Unfavourable 
to  Broca's 
localization 


3°4 


232  CEREBRAL    LOCALIZATION 

The  majority  even  of  the  nineteen  cases  allowed 
by  these  writers  they  consider  to  be  inconclusive 
for  various  reasons. 

Two  cases  of  Burckhart's  are  of  sufficient  surgical 
interest  to  be  worth  quoting.  In  the  first,  he  removed 
5  grams  of  grey  matter  from  the  foot  of  the  first  and 
second  left  temporal  gyri,  but  no  word-deafness 
resulted.  Eight  months  later  he  resected  the  cap 
and  foot  of  the  left  third  frontal  gyrus  (Broca's 
convolution),  but  no  aphasia  followed.  In  the  second 
case  he  resected,  in  several  operations,  the  left 
supramarginal,  temporal,  and  third  frontal  gyri, 
but  he  failed  to  induce  any  speech  defect.  The 
patients  were  demented,  with  verbal  delusions  and 
logorrhcea. 

Marie  maintains  further  that  all  patients  with 
aphasia  are  mentally  deficient ;  thus,  the  cook  can 
no  longer  compound  an  omelette,  and  the  pianist 
can  no  longer  play  the  piano.  He  locates  all  the 
speech  functions  diffusely  in  the  left  temporo- 
parietal region,  maintaining  that  this  is  merely  a 
region  of  intelligence  specialized  for  language,  and 
not  a  storehouse  of  sensory  images  ;  a  mild  lesion 
destroys  the  function  last  acquired,  viz.,  reading, 
and  a  severer  lesion  produces  loss  of  voluntary 
speech  and  of  recognition  of  spoken  language  as  well. 
What  Marie  calls  "  anarthria  " — a  word  previously 
used  in  another  sense — meaning  loss  of  the  power  to 
utter  speech,  although  the  individual  can  say  the 
words  over  to  himself,  is  due  to  a  lesion  in  "  the 
quadrilateral,"  bounded  in  front  and  behind  by  the 
anterior  and  posterior  limiting  sulci  of  the  island  of 


CEREBRAL    LOCALIZATION  233 

Reil,  internally  by  the  wall  of  the  lateral  ventricle, 
and  externally  by  the  surface  of  the  island  of  Reil. 
In  most  cases  of  so-called  Broca's  aphasia,  both  the 
temporal  cortex  and  the  "  quadrilateral "  are 
injured. 

Defenders  of  the  classical  view,  Dejerine  in  par- 
ticular, have  replied  by  advancing  fresh  cases  with 
a  lesion  in  Broca's  gyrus  with  aphasia  resulting  ; 
they  contend  that  Marie's  "  quadrilateral "  contains 
the  projection  fibres  of  the  third  frontal  convolution, 
which  in  their  view  explains  the  anarthria  ;  and  they 
maintain  that  most  of  the  fifty-seven  cases  of  aphasia 
in  which  Broca's  convolution  was  intact  were 
associated  with  much  defect  in  understanding 
language  spoken  or  written,  and  that  the  lesion  was 
one  of  the  dominant  auditory  word  centre  in  the 
temporal  lobe,  without  which  Broca's  convolution 
cannot  work. 

If  it  were  proved  that  in  cases  of  apraxia,  previously 
referred  to,  the  lesion  was  in  the  first  frontal  con- 
volution for  the  legs,  and  in  the  second  frontal  for 
the  arms,  the  location  of  speech  just  in  front  of 
the  motor  centres  for  the  face  and  mouth  would 
receive  strong  support  by  analogy,  but  all  this  is 
still  very  uncertain. 

To  sum  up,  we  may  express  current  opinion  by 
accepting  the  existence  of  a  large  diffuse  centre  in 
the  left  temporo-parietal  region  in  which  recognition 
of  spoken  and  written  language  and  "  internal 
speech  "  take  place  ;  when  it  is  seriously  damaged 
these  are  all  lost  and  the  intelligence  is  impaired. 
Whether  there  is  a  special  departure  platform  in 


234  CEREBRAL    LOCALIZATION 

Broca's  convolution  for  uttering  speech  is  uncertain, 
but  probably  there  is.  Lesions  of  the  projection 
fibres  from  the  cortex  (  (?)  of  Broca's  convolution) 
will  cause  "  anarthria,"  that  is,  loss  of  external  but 
not  of  internal  speech. 

Practical  deductions  are  not  to  trust  aphasia  as 
conclusive  localizing  evidence  of  a  lesion  in  the  left 
third  frontal  gyrus,  but  rather  to  look  to  the  temporal 
region,  especially  if  there  is  any  defective  appreciation 
of  what  is  said  or  written.  Patients  with  left  tem- 
poro-sphenoidal  abscess,  for  instance,  are  usually 
unable  to  name  correctly  objects  shown  them.  More- 
over, we  receive  encouragement  that  there  is  no  need 
to  fear  that  small  cortical  injuries  inflicted  by  the 
surgeon  will  cause  aphasia  ;  subcortical  injuries  are 
much  more  likely  to  do  so,  by  cutting  off  projection 
fibres. 

MISLEADING     LOCALIZING     SIGNS     OF     INTRA- 
CRANIAL    TUMOUR. 

It  is  very  disappointing  when  definite  signs  usually 
regarded  as  of  importance  in  localization  give  colour 
to  a  diagnosis  as  to  the  position  of  a  cerebral  tumour, 
but  on  the  operation  table  nothing  is  found  in  that 
region.  It  is  more  than  disappointing,  because  un- 
successful attempts  to  find  the  tumour  are  more  fatal 
than  actual  removals.  Some  study  therefore  of  the 
physiology  of  the  production  of  misleading  signs  may 
be  useful. 

The  principal  traps  are  furnished  by  the  following  : 

i.  Cranial  Nerve  Palsies. — Paralysis  of  one  or 

both  sixth  cranial  nerves  is  quite  common,  and  by 


CEREBRAL    LOCALIZATION  235 

no  means  proves  that  the  nerve  itself  or  its  nucleus  is 
involved  in  the  lesion.  It  has  been  accounted  for  by 
stretching,  due  to  a  supposed  backward  displacement 
of  the  whole  brain  late  in  the  development  of  a 
growth  ;  the  abducent  nerves  run  straight  forwards 
and  are  slender,  so  the  first  sign  of  the  displacement 
is  a  convergent  squint. 

Other  cranial  nerves,  including  the  third,  fifth, 
seventh,  and  eighth,  are  occasionally  affected  by  dis- 
placements of  the  brain  or  by  pressure. 

2.  Localized  or  General  Convulsions. — Mis- 
takes are  particularly  apt  to  arise  if  the  fit  starts  in 
some  definite  area,  follows  a  slow  and  orderly  march 
to  other  areas,  and  perhaps  affects  only  one  side, 
consciousness  being  lost  late  if  at  all  (Jacksonian 
epilepsy).  It  must,  however,  be  remembered  that 
all  this  may  occur  without  any  obvious  cortical 
lesion  ;  indeed,  the  commonest  cause  of  a  localized 
convulsion  is  ordinary  idiopathic  epilepsy. 

Again,  localized  or  general  convulsions  may  give  a 
wrong  impression  when  arising  late  in  the  course  of 
an  intracranial  tumour  or  abscess,  especially  if  it 
presses  on  the  ventricular  system  of  the  brain  and 
dams  back  the  cerebrospinal  fluid,  causing  hydro- 
cephalus. The  accumulation  of  fluid  in  one  or  both 
lateral  ventricles  stretches  the  overlying  cortex,  and 
may  give  rise  to  fits,  sometimes  of  a  Jacksonian 
type. 

3.  Bilateral  Spastic  Paresis. — In  many  cases  a 
hint  is  given  of  the  true  nature  of  these  seizures  by 
the  presence  of  a  slight  degree  of  bilateral  spastic 
paresis,  with  clumsiness  of  movement,  exaggerated 


236  CEREBRAL    LOCALIZATION 

reflexes,  extensor  plantar  response,  and  a  little 
rigidity. 

Of  course,  if  this  should  chance  to  be  associated 
with  paralysis  of  a  cranial  nerve,  such  as  the  sixth, 
the  temptation  to  diagnose  a  lesion  of  the  pons  would 
be  very  great.  Fortunately,  this  would  not  be  of 
much  surgical  importance,  as  the  pons  is  not  an 
accessible  structure.  Pontine  tumours  are  often 
unilateral,  and  optic  neuritis  is  usually  absent ; 
whereas  in  the  class  of  cases  we  are  now  considering, 
optic  neuritis  is  marked  and  old-standing,  and  there 
is  a  long  history  of  headache,  vomiting,  or  other  signs, 
previous  to  the  development  of  spasticity  or  cranial 
nerve  palsy. 

In  other  cases,  misleading  localizing  signs  may 
arise  from  patches  of  secondary  thrombosis,  spreading 
oedema,  or  meningitis  ;  but  none  of  these  is  common. 

The  suspicious  feature  about  all  the  signs  here 
mentioned  is  their  late  development.  Localizing 
symptoms  appearing  when  headache,  vomiting,  optic 
neuritis,  or  other  evidences  have  been  present  for 
months  or  years  are  little  to  be  trusted.  Early 
localizing  signs,  on  the  other  hand,  are  trustworthy 
in  the  main. 

A  few  words  may  be  said  about  the  significance 
of  ataxia.  This  is  of  course  evidence  of  a  lesion  of 
the  cerebellum,  but  it  may  be  seen  in  other  conditions 
also.  Putting  aside  ataxia  due  to  affections  of  the 
labyrinth,  Friedreich's  ataxia,  and  other  general 
nervous  diseases,  it  may  also  be  caused  by  a  tumour 
in  the  neighbourhood  of  the  red  nucleus  in  the 
isthmus,  or  in  the  pons. 


CEREBRAL    LOCALIZATION  237 

THE     CEREBROSPINAL     FLUID. 

This  fluid  is  clear,  watery,  and  of  low  specific 
gravity ;  it  contains  almost  no  albumin,  but  some 
sugar.  Until  recently  this  reducing  substance  was 
thought  to  be  a  pyrocatechin  body.  It  contains  no 
cells  in  health,  nor  does  it  contain  the  antitoxins, 
opsonins,  or  alexins  which  are  present  in  plasma, 
lymph,  and  most  serous  fluids.  This  explains  the 
great  liability  to  septic  meningitis  after  injuries  to 
or  operations  on  the  central  nervous  system.  As 
urotropin  is  excreted  into  the  cerebrospinal  fluid 
when  given  by  mouth,  it  may  usefully  be  administered 
to  prevent  septic  complications  such  as  the  above, 
or  following  on  suppurative  otitis  media.  Some 
success  is  already  claimed  for  this  procedure. 

The  fluid  is  secreted  by  the  choroid  plexus  into  the 
lateral  and  third  ventricles  ;  it  passes  by  the  Sylvian 
aqueduct  into  the  fourth  ventricle,  escapes  by  the 
foramina  in  the  roof  into  the  subarachnoid  space, 
and  is  absorbed,  partly  by  the  aid  of  the  Pacchionian 
bodies,  into  the  superior  longitudinal  sinus  and  other 
veins.  Hydrocephalus  is  produced  by  blocking  of 
the  foramina  in  the  roof  of  the  fourth  ventricle.  If 
an  exit  is  provided,  large  quantities  of  cerebrospinal 
fluid  may  be  lost  daily. 

Lumbar  puncture  is  a  very  valuable  aid  to  dia- 
gnosis in  various  forms  of  meningitis,  parasyphilitic 
affections,  etc.,  and  the  fluid  may  be  blood-stained 
after  cerebral  haemorrhage  or  injury.  It  is  also 
valuable  in  treatment  as  a  means  of  reducing  intra- 
spinal and  intracranial  pressure,  particularly  if  the 
trouble  lies  below  the  tentorium. 


238  CEREBRAL    LOCALIZATION 

REFERENCES. 

Cushing  and  Bordley. — "  Observations  on  Experimentally 
Induced  Choked  Disc."    Bulletin  Johns  Hopkins  Hospital, 

1909,  xx,  p.  95. 

Horsley. — "  Optic    Neuritis."      British     Medical    Journal, 

1910,  i,  p.  553. 

Horsley  and  Clarke. — "  The  Structure  and  Functions  of 
the  Cerebellum."     Brain,  1908,  xxxi,  p.  45. 

Thiele. — "  The  Optic  Thalamus  and  Deiters'  Nucleus." 
Journ.  of  Physiology,  1905,  xxxii,  p.  358. 

Allen  Starr. — "Tumours  of  the  Acoustic  Nerve."  Amer. 
Journ.  of  Medical  Sciences,  1910,  cxxxix,  p.  551. 

Bergmark. — "  Cerebral  Monoplegia."  Brain,  1909,  xxxii, 
p.  342. 

Cushing. — "  A  Note  on  Faradic  Stimulation  of  the  Post- 
central Gyrus  in  Conscious  Patients."  Brain,  1909, 
xxxii,  p.  44. 

Wilson. — "  A  Contribution  to  the  Study  of  Apraxia." 
Brain,  1908,  xxxi,  p.  164. 

Collier. — "  Recent  Work  on  Aphasia."  Brain,  1908,  xxxi, 
P-  523. 

Collier. — "  The  False  Localizing  Signs  of  Intracranial 
Tumour."     Brain,  1904,  xxvii,  p.  490. 

Head  and  G.  Holmes. — "  Researches  as  to  Sensory  Disturb- 
ances from  Cerebral  Lesions."  Lancet,  1912,  i,  pp.  1, 
79,  144- 


239 


CHAPTER    XIV. 

THE    ACTION    OF    CUTANEOUS 
ANESTHETICS. 

DRUGS    APPLIED    TO    THE    UNBROKEN    SKIN. 

IT  has  been  customary  to  relieve  abdominal  pain 
by  the  application  of  hot  fomentations  containing 
opium,  to  treat  sprains  and  bruises  with  lead  and 
opium,  and  to  smear  on  glycerin  of  belladonna  for 
the  discomfort  of  white  leg.  What  dyspeptic  old 
lady  has  not  worn  a  belladonna  plaster  over  her 
heart,  and  what  practitioner  has  not  prescribed  a 
belladonna  liniment  for  vague  aches  and  pains  ? 
The  rationale  of  the  treatment  has  been  that  bella- 
donna, opium,  and  menthol  are  alleged  local 
anaesthetics,  and  it  is  further  supposed  that  they  are 
absorbed  by  the  unbroken  skin.  The  truth  is  that 
they  are  not  local  anaesthetics,  and  that  they  are 
scarcely  if  at  all  absorbed  through  the  unbroken 
skin.  Neither  aconite,  cocaine,  carbolic  acid,  bella- 
donna, nor  opium  has  any  power  to  relieve  pain 
when  applied  to  normal,  healthy  skin. 

It  has  been  well  said  that  "  You  have  not  proved  a 
lie  to  be  a  lie,  until  you  have  shown  how  it  came  to 
be  believed."  This  is  very  true  in  science,  and 
especially  in  medical  science.  The  use  of  belladonna 
and  opium  to  relieve  local  pain  was  an  obvious 
deduction  from  their  great  power,  when  given  by  the 


240  THE    ACTION    OF 

mouth,  to  relieve  general  pain  by  inducing  sleep  or 
allaying  colicky  contractions.  In  the  case  of  bella- 
donna and  its  alkaloid  atropine,  the  fallacy  was  the 
more  natural  in  that  they  have  a  very  genuine  effect 
in  paralysing  nerve-endings,  but,  unfortunately,  it  is 
only  the  efferent  nerve-endings  in  glands  and  unstriped 
muscle  that  are  paralysed,  not  the  sensory  twigs  in 
the  skin. 

The  fallacy  has  been  maintained  by  the  practice  of 
combining  these  drugs  with  other  and  more  potent 
treatment ;  thus,  belladonna  is  given  with  counter- 
irritants  such  as  camphor  or  alcohol ;  warmth  may 
be  applied  with  the  opium ;  friction  helps  the  bella- 
donna liniment  to  keep  its  reputation,  and  even  the 
support  of  the  strapping,  with  counter-irritants  in 
it,  assists  the  patient  to  believe  in  the  value  of  a 
belladonna  plaster. 

We  may  go  one  step  further,  and  say  that  the 
application  of  opium  and  belladonna  to  mucous 
membranes  is  equally  futile.  There  is  no  evidence 
that  opium  suppositories  after  the  operation  for 
piles,  or  laudanum  dropped  into  aching  ears,  have 
any  direct  local  effect.  Of  course,  morphia  may  be 
absorbed  from  the  suppository,  but  in  that  case  it 
presents  no  advantage  over  a  dose  given  by  mouth 
or  hypodermically,  and  is  less  certain  in  its  action. 

To  sum  up,  there  is  no  drug  in  common  use  capable 
of  acting  as  an  anaesthetic  on  the  unbroken  skin, 
except  ether  and  ethyl  chloride,  which  freeze  it,  and 
the  only  drugs  which  relieve  deep-seated  pain  when 
painted  on  or  rubbed  into  the  skin  are  the  counter- 
irritants. 


CUTANEOUS    ANESTHETICS  241 

Full  details  of  the  experimental  data  for  these 
conclusions,  which  are  accepted  by  the  leading 
pharmacologists,  will  be  found  elsewhere.  Briefly, 
the  methods  adopted  were  as  follows. 

Strong,  even  dangerously  strong  solutions  and 
ointments  containing  opium,  atropine  or  belladonna, 
aconite,  cocaine,  carbolic  acid,  and  menthol  were 
rubbed  into  the  skin  of  the  finger,  and  on  the  tongue, 
and  these  were  then  examined  to  see  if  their  sensi- 
bility was  in  any  way  altered.  The  methods  of 
examining  the  skin  of  the  finger  were  as  follows. 
Each  test  was  applied  on  more  than  one  observer 
and  after  varying  intervals  of  time. 

1.  The  Intolerable  Temperature  Test. — For  each 
observer  there  was  a  certain  constant  temperature 
which  was  just  not  intolerably  hot  when  the  finger 
was  dipped  into  warm  water  for  half  a  minute. 
This  was  determined  before  and  after  applying  the 
drug  under  consideration. 

2.  The  Faradic  Pain  Test — The  strength  of  current 
was  determined,  before  and  after  the  application  of 
each  drug,  at  which  the  damp  finger  first  found 
electrical  stimulation  by  means  of  electrodes  led 
off  from  a  faradic  coil  actually  painful,  the  current 
used  being  small  at  first  and  gradually  augmented. 

3.  Thermal  Discrimination  Test. — We  found  that 
we  were  able,  by  immersing  the  finger  first  in  one 
beaker  of  warm  water  and  then  in  another,  to  detect 
a  difference  in  temperature  of  not  less  than  one  degree. 
This  was  tested  before  and  after  the  application  of 
each  drug. 

4.  General  Testing  by  means  of  a  pin  point,  the 

16 


242  THE    ACTION    OF 

aesthesiometer,  a  wool  pencil,  etc.,  was  also  used. 
In  testing  the  sensibility  of  the  tongue,  we  used  the 
faradic  pain  test  as  described  above  ;  we  examined 
thermal  discrimination  by  applying  warm  metal 
points  at  various  temperatures  ;  we  used  the  aesthesio- 
meter, and  studied  the  effect  of  the  drugs  on  taste. 

Judged  by  these  standards,  the  various  drugs  fared 
as  follows  : — 

Opium. — A  5  per  cent  solution  of  morphine 
tartrate  in  water  had  no  effect  on  skin  or  tongue. 

Belladonna. — Very  strong  liniments  had  no  anaes- 
thetic effect.  Indeed,  if  they  had,  the  drug  could 
be  used  instead  of  cocaine  for  eye  surgery.  The  only 
sign  we  could  obtain  was  diminution  of  sweating 
over  the  skin  area  treated.  There  was  no  flushing 
or  blanching  of  the  skin  or  mucous  membrane. 

Aconite. — Neither  the  B.P.  liniment  nor  ointment 
had  any  effect  on  the  skin.  Solutions  produced 
tingling  of  the  tongue,  but  we  were  not  quite  confident 
whether  there  was  or  was  not  a  little  reduction  in 
sensibility. 

Cocaine. — Strong  ointments  and  alcoholic  solutions 
had  no  effect  on  the  unbroken  skin.  Of  course,  if 
the  skin  is  damaged,  the  effect  is  marked.  A  10  per 
cent  solution  applied  to  the  tongue  produced  con- 
siderable reduction  of  sensibility,  by  all  our  tests. 

Menthol  produces  a  curious  stimulation  of  the 
nerve-endings  which  detect  cold,  as  is  well  known. 
A  discussion  of  its  other  actions  would  lead  us  too 
far,  but  any  anaesthetic  effect  is  purely  that  of  a 
counter-irritant. 

Carbolic  Acid  rather  increases  the  sensitiveness  of 


CUTANEOUS     ANESTHETICS  243 

the  finger  to  painful  stimuli.  Its  undoubted  value 
in  relieving  toothache  is  due  to  its  caustic  action  in 
destroying  irritated  nerve-endings.  The  numb  feel- 
ing we  get  after  prolonged  soaking  in  I  in  20  carbolic 
is  due  to  the  formation  of  a  thin  coating  of  killed 
epidermis  over  the  hands. 

The  fact  that  even  cocaine,  which  is  thoroughly 
proved  to  paralyse  sensory  nerves,  fails  to  produce 
the  slightest  effect  when  a  10  per  cent  solution  in 
alcohol,  or  a  10  per  cent  ointment  made  with  lanolin, 
is  rubbed  into  the  skin,  is  strong  evidence  that  little 
if  any  of  these  alkaloids  reaches  the  nerve-endings 
at  all.  Atropine  finds  its  way  into  the  sweat  ducts 
sufficiently  to  reduce  but  not  to  abolish  sweating 
by  its  action  on  the  sweat  glands.  It  is  true  that 
cases  of  poisoning  from  the  application  of  belladonna 
to  the  skin  are  recorded,  but  only  where  there  were 
abrasions  or  sores  present,  or  perhaps  in  young 
children  whose  skin  is  very  delicate. 

It  may  be  objected  that  there  is  sufficient  clinical 
evidence  of  benefit  from  these  drugs  to  defy  negative 
results  by  experimental  methods,  but  any  who  claim 
this  must  not  confuse  the  issue  by  combining  the 
belladonna  or  opium  with  camphor,  heat,  rest,  or 
strapping.  Again,  it  may  be  suggested  that  atropine, 
at  least,  has  some  vasomotor  effect,  but  we  failed 
to  observe  any,  and  indeed  we  doubt  if  it  ever  reaches 
the  blood-vessels  when  rubbed  into  the  unbroken  skin. 

It  is  a  thankless  task  to  pull  down  strongholds  of 
belief,  but  it  is  necessary  if  only  to  direct  more 
attention  to  the  true  means  of  giving  relief  to  pain, 
including    general    drug    treatment,    rest,    massage, 


244  CUTANEOUS    ANESTHETICS 

counter-irritation,  heat,  and  passive  hyperemia. 
Moreover,  a  recognition  of  the  failure  of  drugs  saves 
useless  expense,  and  may  banish  from  patients' 
houses  some  of  the  commonest  of  powerful  poisons. 
Belladonna  liniment,  for  instance,  has  been  respon- 
sible for  an  immense  number  of  alarms,  illnesses, 
and  even  fatalities. 

REFERENCE. 

A.  Rendle  Short  and  Walter  Salisbury,  British  Medical 
Journal,  1910,  i,  p.  560. 


245 


APPENDIX. 


ABSORPTION  OF  NITROGEN  FROM 
AMINO-ACIDS. 
We  have  made  several  observations  on  patients  "fed  " 
with  nutrients  of  milk  digested  with  pancreatic  extract  for 
twenty-four  hours  in  an  incubator,  so  as  to  convert  most 
of  the  protein  into  aminoacids.  Such  nutrients  are  not 
irritating.  An  example  of  such  a  case  is  the  following 
(I  am  indebted  to  Mr.  P.  A.  Opie  and  to  Dr.  Bywaters 
for  some  of  the  analyses). 

Case  I. — A.  H.,  aged  25,  female,  suffering  from  vomit- 
ing and  gastric  pain,  not  relieved  by  a  diet  of  peptonized 
milk,  was  put  on  nutrient  enemata  as  follows  : — 

March  28-29. — By  mouth  ;   water. 

By    rectum  ;     saline,    15    ounces    three 
times  a  day. 
March  29- April  1. — By  mouth  ;    water. 

By  rectum  ;    6   per  cent  glucose, 
1  pint  three  times  a  day. 
April  1-4. — By  mouth  ;    water. 

By  rectum  ;    milk  digested  for  twenty-four 
hours,  six  ounces  every  four  hours. 
April  4. — By  mouth  ;    peptonized  milk. 


Urine  in 

Ammonia  N. 

Daily  output  of 
N.  in  urine 

ounces 

per  cent 

in  grams. 

March  28-29 

29 

8-o3\ 

29-30 

22 

3'2 

6-28  [  Av. 

30-31 

26 

o-8 

4-36  [6-04 

3 1 -April  1* 

26 

12-3 

5-56' 

April  1-2 

16 

12-7 

7-66)Av. 

„       2-3 

22 

12-5 

5'91    7-70 
9'53)  '  ' 

3-4 

32 

9-3 

4-5 

31 

o'5 

9-02 

*  Glucose  not  well  retained. 


246 


APPENDIX 


It  will  be  observed  that  instead  of  showing  the  usual 
steady  fall,  the  nitrogen  output  is  increased  during  the 
three  days  of  feeding  on  aminoacids. 

Case  II. — This  patient,  a  man,  was  fed  as  follows, 
the  daily  output  of  nitrogen  in  the  urine  being  also 
shown  : — 


By  mouth 

By  rectum 

Urine  in 
ounces 

Ammonia 
N.  per  cent 

Daily  output 

of  N.  in  urine 

in  grams 

April 

26-27 

Milk 

Nil 

21 

1*4 

14*3 

27-28 

Water 

Saline 
(  Milk  pepto- 

19 
) 

29 

10-7 

28-29 

nized  20 

>> 

1    minutes ; 

21 

3*5 

9'6 

(§v  6-hourly 

J 

29-30 

>> 

,, 

20 

4-8 

6-8 

30-May    1 

>> 

11 

'  Milk  pepto- 

16 

) 
,10 

2-9 

7-9 

May 

nized  24 
hours,  §v 
6-hourly, 

1-2 

>> 

2-9 

7-2 

with  3j  of 

L     glucose 

i 

2-3 

tt 

>» 

21 

3-o 

14-4 

3-4 

;  Pept. 

>> 

) 

15 

37 

II-2 

4-5 

milk 
§v  2- 

I      Nil 

23 

2-8 

i6-i 

hourly 

C   Milk 

[       Nil 

5-6 

54 

0-9 

137 

( hourly 

As  the  accompanying  chart  shows,  the  absorption  and 
output  of  nitrogen  are  very  considerably  increased  when 
the  milk  has  been  digested  with  pancreatic  extract  for 
twenty-four  hours.  The  increased  absorption,  as  usual, 
does  not  increase  the  output  for  about  twenty-four 
hours. 


APPENDIX 


247 


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<  15 

o  14 

Z  13 

z«2 

S" 
o  io 

Cu 

«           w 

o   7 
56 

&  s 

3* 
S3 

=!   2 

2  i 

DAY     OF    FAST. 

1 

2 

3 

4 

5 

6 

7 

8 

9 

10 

• 

/   V 

I    \ 

« 

* 

\ 

; 

w 

I 

i 
i 

\ 

i 

i 

o. 

> 

-£ 

\ 

/ 

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^ 

ft 

^ 

\ 

/   * 

J 

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Bi 

■ 

m 

^ 

.^: 

SH 

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&& 

>  Case  II. 


>Case  I. 


Case  I. 
Case  II 

Y/////////A  Nutrients  peptonized  20  minutes. 
Nutrients  peptonized  24  hours. 
Mouth  Feeding. 


248 


INDEX 


ABDERHALDEN  on  preg- 
nancy 
Absorption  in  the  colon 

—  of  proteins 
Acapnia  and  shock 
Acetonemia   after   chloroform 

—  conditions  in  which  seen  .  . 

—  treatment  of 
Acetone  in  urine  normally    . . 
test  for . . 

—  origin  of,  from  fat 
Acid  dyspepsia  of  infants 
Acidosis  after  chloroform 

—  conditions  in  which  seen  . . 

—  in  diabetes 

—  treatment  of 
Aconite  as  local  analgesic     . . 
Acromegaly 

—  treatment  of 
Addis  on  haemophilia 
Adhesions,  absorption  of 
Adiposity     from     removal     of 

pituitary  gland 
Adrenalin-chloroform  complex 
Adrenalinoscope 
Albuminuria,  transient,  calcium 

salts  for 
Alcohol  in  shock 
Amino-acids      . .  . .        123, 

Ammonia  nitrogen,  variations 

in 
Anaesthesia,  testing  for 
Anderson  and  Langley  on  re- 
generation of  nerve     . . 
Anoci-association 
Anterior  horn  cell  changes  after 

division      of      posterior 

nerve-roots 
Antithrombin 
Aphasia 
Appendicitis,  hyperchlorhydria 

with        . .  .  .  84,  ri2 

Apraxia.  .  .  .  .  .  . .      228 

Ataxia,  cerebellar        . .  . .      217 

—  not  always  cerebellar       . .     236 

—  from   division   of   posterior 

nerve-roots       . .  . .      199 

Atheroma  in  cretin  animals  . .        73 

—  and  myxcedema     . .  . .       82 


PAGE 

Atropine  for  chloroform  poison- 


19 

ing          

179 

125 

Auditory  nerve,  tumours  of  . . 

219 

122 

26 

—  word  centre 

231 

l8l 
157 

Baldwin,  Helen,  on  oxaluria  . . 

153 

171 

Ballance  on  nerve  anastomosis 

197 

158 

Bar  any  on  nystagmus 

218 

171 

Barlow  on  intravenous  saline 

53 

158 

Bayliss  and  Starling  on  secretin 

118 

112 

Bell,  Blair,  on  menstruation  . . 

8 

l8l 

arrested  uterine  develop- 

157 

ment    . . 

15 

169 

Belladonna  as  local  analgesic 

242 

170 

Beri-beri 

1 

242 

Bergmark  on  cerebral  cortex  . . 

222 

91 

Bile        

r2i 

95 

Bismuth  feeding          . .          98, 

ro6 

137 

Blood-clotting 

131 

134 

Blue     blindness     in     cerebral 

tumour 

215 

93 

Bone,  growth  of 

56 

180 

—  transplantation 

67 

4i 

Bordley  and  Cushing  on  choked 

disc 

213 

144 

jS-oxybutyric    acid,    origin    of, 

49 

from  fat 

159 

127 

in  urine,  test  for 

Boyd  and  Robertson  on  nutrient 

170 

162 

enemata 

128 

241 

Broca's  convolution 

Brown,   Langdon,   on  nutrient 

231 

192 

enemata 

127 

50 

Bulloch  on  haemophilia 
Burckhardt     on     removal     of 

135 

speech  centres 

232 

200 

Burdach's  tract 

202 

133 

Bywaters  on  nutrient  enemata 

127 

230 

Calcium  oxalate  in  urine      . .  152 

—  salts  for  haemophilia         .  .  141 

in  tetany           . .          . .  85 

treatment  by    .  .          . .  144 

Calculus,  prevention  of        151,  154 
Cameron       on       gastrojejuno- 
stomy    .  .          . .          . .  117 

Cancer,  gastric,  HC1  deficient  in  115 


INDEX 


249 


PAGE 

Cannon      on      skiagraphy      of 

stomach            . .          .  .  99 

Cannon  and  Murphy  on  peri- 
stalsis    . .          . .          . .  105 

Carbolic  acid  as  local  anaesthetic  242 
Carbon    dioxide,    relation    to 

shock      . .          . .          . .  26 

Cauda  equina,  tumours  of      .  .  208 

Cerebellar  tracts          . .          . .  202 

Cerebello-pontine     angle,     tu- 
mours of            . .  219 
Cerebellum,  lesions  of .  .          . .  215 

Cerebral  localization   ..          ..  213 

—  tumour,   blue  blindness  in  215 

late  signs  misleading  . .  234 

Cerebrospinal  fluid      . .          . .  237 

Cheyne^  W.,  on  shock  . .          . .  22 

Chilblains,  treatment  of  . .  144 
Chloroform  causing  sudden  death  177 

—  poisoning,  delayed  . .  181 
Choked  disc,  cause  of . .  . .  213 
Chromatolysis  of  anterior  horn 

cells        . .          .  .          . .  200 

—  in  shock      . .          . .          . .  47 

Chromosomes    .  .          .  .          . .  17 

Clarke   and   Horsley   on   func- 
tions of  cerebellum     .  .  215 

Coagulation    of   blood,    physi- 
ology of             131 

Coagulimeter    . .          . .          .  .  133 

Cobbett  on  shock          „          .  .  35 
Cohnheim    on   pancreatic   dia- 
betes     . .          . .          . .  168 

Collier  on  misleading  signs  of 

cerebral  tumour          . .  234 
Colon,  functions  of      . .        104,  125 
Coma,  prolonged  after  chloro- 
form      . .          . .          . .  182 

Concussion  of  the  spinal  cord  210 

Congenital  goitre         . .          .  .  78 

Constipation     ..          ..          ..  106 

Convulsions  in  cerebral  tumour 

226,  235 
Copeman  and  Sherrington    on 

shock      . .          .  .          .  .  36 

Corpus   callosum,    tumours   of  230 

—  luteum         .  .          . .          . .  n 

Cortex,  localization  of  sensation 

in            . .          . .          . .  220 

Cortical   tumours,   localization 

of            . .          . .          . .  225 

Cotter,  Patrick,  the  giant      . .  92 

Cretin  lambs     . .          . .          . .  78 

Cretinism,      experimental,     in 

animals  . .          . .          . .  73 

Crile  on  surgical  shock  22,  47,  49 
Cushing  and  Bordley  on  choked 

disc         . .                       . .  213 

Cushing  on  blue  blindness      ..  215 

—  on  localization  of  sensation 

in  cortex           . .        220,  222 


PAGE 

Cushing  on  removal  of  pituitary  89 

Cyclical  vomiting        ..          . .  158 

Cystin,  origin  of          ..          ..  155 

Davis,  O.  C.  A/.,  on  oxaluria  .  .  152 
Deiter's  nucleus,  influence  on 

tone        . .          . .          46,  217 

Dejerine  on  aphasia  . .  . .  233 
Dextrose,     absorption    of    by 

colon      .  .          . .          .  .  128 

Diabetes,  causation  of           . .  163 

Diabetic  coma,  prevention  of  173 

treatment  of     . .          . .  176 

Diabetics,  operations  on  .  .  175 
Diacetic  acid,  origin  of,  from 

fat          159 

in  urine,  test  for         . .  171 

Diagnosis  of  starvation          . .  163 

Diuretic,  pituitary  extract  as  a  96 

Duhamel's  ring  experiment    . .  58 


Edmunds  on  goitre     . .          . .  76 

myxoedema       . .          .  .  71 

parathyroids     . .          . .  72 

tetany    .  .          . .          . .  85 

Eiselsberg     on      experimental 

cretinism           . .  . .  73 

Enemata,  nutrient      . .  126,  245 

Epicritic  sense..          ..          ..  185 

Erepsin.  .           . .          . .          . .  123 

Exophthalmic  goitre  . .          . .  83 

due  to  iodoform          . .  81 

Exophthalmos    from     thyroid 

feeding  . .          . .          . .  74 

Exostoses          . .          . .          . .  65 


Faciai,  palsy,  treatment  of  .  . 
Fawcett  on  skeleton  of  a  giant 
Fenwick,     Soltau,     on    hyper- 

chlorhydria 
Fibrinogen 
Fibrinolysis 
Forssman   on   regeneration   of 

nerve 
Fractures,  repair  of 
—  treatment  of 
Frdhlich's  symptom  complex 
Frontal  cortex,  functions  of  . 
Funk  on  vitamines 


197 
92 

115 
132 

134 

194 
64 
65 
93 

225 
2 


Gastric  ulcer,  cause  of  ..  in 

hyperchlorhydria  in  83,  no 

Gastrojejunostomy,    course  of 

food  after         . .  . .  116 

—  nutrition  after        ..  ..  117 

Gastrostaxis      ..          ..  ..  115 

Gastrostomy,  feeding  after  ..  118 

Gigantism         ..          ..  ..  91 


250 


INDEX 


Glucose,  relation  to  acidosis  . 

Gh'cosuria 

Goitre,  causation  of    . . 

—  iodothyrin  in 

—  relation  to  drinking  water 

—  treatment  of 

Goll's  tract 

Goodman    on    transfusion    for 

haemophilia 
Grafting  for  myxoedema,  ere' 

tinism,  or  tetany 
Graves'  disease 

caused  by  iodoform 

treatment  of    . . 

Gray  and  Parsons  on  shock 
Groves,  Hey,  on  bone  . . 

the  colon 

Griinbaum,    on    saline    trans 

fusion 
Guanin 


PAGE 

160 

163 
75 
77 
75 
84 

202 

142 

85 
83 
81 

85 

25 

63 

125 

53 
149 


HiEMATEMESIS  .  .            ..             ..  115 

—  treatment      by      nutrient 

enemata             . .        126,  245 

Haemophilia,  pathology  of     . .  136 

—  treatment  of           . .  140 
Haemorrhage  into  spinal  cord  21  r 

membranes              . .  211 

Haemorrhages,  profuse           . .  131 
Hemorrhagic  diathesis,   cause 

of            ..          ..          ..  136 

Hall,  Walker,  on  the  colon    . .  126 

the  purinometer          . .  152 

Halliburton    and    Mott   on   re- 
generation of  nerve     .  .  193 
Harrison,  Ross,  on  developing 

nerve  fibres      . .          . .  193 
Head  on  cutaneous  sensation  185 
Head  and  G.   Holmes  on  sen- 
sation in  brain .  .          . .  224 
Headache,  lymphatic,  calcium 

salts  for  . .  . .  144 
Heape  on  menstruation  . .  8 
Hearing,  cortical  localization  of  220 
Heart,  massage  of,  for  chloro- 
form poisoning  .  .  179 
Hemianesthesia,  not  cortical  222 
Henderson,  Y.,  on  shock  . .  26 
Hertz  on  gastric  sensation  . .  108 
*—  skiagraphy   of   stomach   . .  99 

—  ileocaecal  sphincter            . .  103 
Holmes,  G.,  and  Head,  on  sensa- 
tion in  brain     .  .          . .  224 

Hopkins  on  vitamines             . .  3 

Horsley  and  Clarke  on  func- 
tions of  cerebellum     ..  215 

Hort    and    P enfold    on    saline 

transfusion        . .          . .  52 

Hour-glass  stomach,  diagnosis 

of           ..          ..          ..  102 


PAGE 

Hunger-pain     ..          ..          ..  112 

Hunt  and  Seidel  on  iodothyrin  77 

Hydrocephalus,  pathology  of  237 
Hydrochloric  acid,  deficient  in 

gastric  juice     . .          . .  115 

variations  in  stomach. .  109 

Hyperchlorhydria        ..          ..  no 


Ileocecal  sphincter..         ..  103 

Ileosigmoidostomy,  a  draw- 
back of . .          . .          . .  105 

Infantile  palsy,  nerve  anasto- 
mosis for           . .          . .  197 

Infantilism    from    removal    of 

pituitary  gland            . .  94 

Intestinal  paralysis,  treatment  of  1 06 

—  peristalsis,  arrest  of  . .  105 
Intestine,  functions  of  large  104,  125 
Intravenous  saline  transfusion  51 
Iodides,    action   on   gummata 

and  atheroma  . .          . .  86 

—  for  goitre    . .          . .          . .  84 

Iodine  in  foodstuffs     . .          . .  78 

— .  in  thyroid  . .          .  .          . .  74 

Iodoform  poisoning     . .          . .  80 

Iodothyrin        . .          . .          . .  '74 


Jacksonian  epilepsy             . .  235 
Jackson-Taylor's  test  for  ace- 
tone      . .          . .          . .  171 

Knowlton  and  Starling  on  dia- 
betic heart        . .          . .  168 
Kocher  on  tetany        . .          . .  84 

the  thyroid       . .          . .  71 

Kropfbrunnen  ..          . .          . .  76 

Labyrinth  and  nystagmus  . .  218 

Lactation,  cause  of      . .          . .  16 
Laidlaw  and  Ryffel  on  nutrient 

enemata            ..          ..  126 
Langley  and  Anderson  on  re- 
generation of  nerve     .  .  192 

nerve  anastomosis       .  .  197 

Leukaemia,  uric  acid  in          . .  150 
Levy  on  chloroform  poisoning 

178,  180 

Liepmann  on  apraxia  . .          . .  228 

Localization,  cerebral             . .  213 
Lossen  and  Morawitz  on  haemo- 
philia    . .          . .          . .  136 

L,umbar  puncture  in  diagnosis  237 

Lyon  and  Seelig  on  shock       . .  24 

Macallum  on  tetany    . .          .  .  85 

McCarrison  on  goitre .  .          . .  79 

Macewen  on  growth  of  bone  . .  57 


INDEX 


251 


PAGE 

Magnesium  salts,  treatment  by  144 

Magnus-Levy  on  acidosis       ..  159 

—  thyroid  feeding  . .  . .  74 
Malcolm  on  shock  . .  . .  23 
Marie  on  aphasia  ..  ..  231 
Marine  on  cretin  lambs  . .  76 
Marshall  on  menstruation  . .  8 
Mayo  on  Graves'  disease       . .  86 

hyper chlorhydria         .  .  12 

Mellanby  on  blood-clotting   . .  132 

Meningitis,  prevention  of       .  .  237 

Menopause,  treatment  of       . .  144 

Menstruation    . .          . .          . .  7 

Menthol  as  local  analgesic     . .  242 

Milk,  secretion  of        . .          . .  16 

—  and  scurvy . .          . .          .  .  4 

Miller,      Reg.,      on      infantile 

dyspepsia          . .          .  .  in 

Misleading  localizing  signs  of 

cerebral  tumour          . .  234 

Mitosis  . .          . .          . .          . .  18 

Monakow's  bundle      . .          . .  201 

Monoplegia       from       cortical 

tumours             . .          . .  226 

Moore,  B.,  on  calculi  . .          . .  154 

Morawitz  and  Lossen  on  haemo- 
philia     ..          ..          ..  136 

Mott   and,    Halliburton   on   re- 
generation of  nerve     . .  193 
Movements  of  stomach          . .  100 
Murray    on    myxcedema    and 

cretinism           . .          . .  69 

Murray    and    Warrington    on 
nerve    anastomosis    for 

infantile  palsy . .          ..  198 

Mummery  on  surgical  shock  . .  22 
Murphy  and  Cannon  on  peri- 
stalsis    . .          . .          . .  105 

Myositis  ossificans       . .  64,  65 

Myxoedema  and  atheroma     . .  82 

—  experimental           . .          . .  71 

—  treatment  of           . .          . .  84 

Nerve  anastomosis    . .          . .  197 

—  cells  in  shock          . .          . .  47 

—  grafting        . .          . .          . .  196 

—  injuries,  effects  of  .  .  . .  184 
regeneration      . .          . .  189 

—  roots,  development  of  .  .  193 
distribution,  table  of  206,  207 

—  — -  effects  of  division  of  . .  199 
surgical   indications  for 

dividing  posterior     . .  210 

—  section,  effects  of  incomplete  189 

—  suture,  in  bridging  gaps  .  .  196 
recovery  after  . .          . .  189 

—  transplantation  . .  .  .  196 
Newt,  regeneration  in  the  ..  211 
Nissl's  degeneration  in  anterior 

horn  cells  after  division 

of  posterior  nerve-roots  200 


PAGE 

Nitrogen   output   on   nutrient 

enemata             . .         127,  245 
Novocain  injected  into  nerves 

to  prevent  shock         . .  50 

Nucleoprotein  and  purin  bodies  146 

Nutrient  enemata        . .         126,  245 

Nystagmus       . .          . .          . .  218 

O'Byrne,  Patrick,  the  giant. .  92 

Occipital  lobe,  function  of  . .  221 
CBdema  of  lungs  from  saline 

transfusion        . .          . .  53 

(Esophagus,  movements  of    . .  99 

Oligaemia  and  shock   . .          .  .  35 

Olive  oil,  action  on  bile  flow  . .  122 

Operations  on  diabetics          . .  175 

Opium  as  local  analgesic        . .  242 

Optic  neuritis,  cause  of         . .  213 

—  thalamus,  lesions  of          . .  225 
Ord  on  myxcedema     . .          .  .  69 

Osier,  cases  of  haemophilia     . .  135  n. 

Ovary     . .          . .          . .          . .  7 

Ovulation          . .          . .          . .  8 

Ovum,  maturation  of . .          . .  17 

Oxaluria            . .          . .          . .  152 

—  prevention  of         . .          . .  154 

Pain  sense,  conduction  in  spinal 

cord        . .          . .          . .  154 

Pancreatic  diabetes     ..          ..  165 

—  fistulae          . .          . .          . .  122 

—  juice,  secretion  of  . .  . .  118 
Parathyroids     .  .          . .          . .  72 

—  effects  of  removal  of  .  .  72 
Parsons  and  Gray  on  shock  . .  25 
Passler  and  Romberg  on  toxaemic 

shock      . .          . .          . .  31 

Pater  son  on  gastrojejunostomy  117 

hydrochlorhydria         ..  112 

Paulesco  on  removal  of  pitui- 
tary          89 

Pawlow  on  pancreatic  secretion  118 

—  peristalsis   . .          . .          . .  105 

Penfold  and  Hort  on  saline  trans- 
fusion    .  .          . .          .  .  52 

Periosteum  forming  bone  . .  60 
Periostitis          . .          . .            59,  66 

Peristalsis  in  colon     . .          .  .  104 

—  gastric          . .          . .          . .  100 

—  and  C02      . .          . .          . .  30 

Phloridzin  and  glycosuria  . .  164 
Physostigmine    for    intestinal 

palsy      .  .          . .          . .  106 

Pike  on  spinal  shock    .  .          . .  44 

Pineal  gland      .  .           . .           . .  96 

Pituitary  extracts,  feeding  or 

injecting  with  . .  91,  9 6 

for  shock  . .  49,  96 

- —  gland,  effects  of  removal  of  89 

functions  of      . .          . .  88 

structure  of      . .          . .  88 


252 


INDEX 


Pituitary  gland,  operations  for 

removal  of          . .          . .  95 

Pons,  tumours  of        . .          . .  236 

Post-central  convolution,  func- 
tion of  .  .          . .          . .  221 

Posterior  columns  of  Goll  and 

Burdach             . .          .  .  202 

Posterior  nerve  roots,  effects  of 

division  of        . .          . .  199 

surgical    indications 

for  dividing      .  .          .  .  200 
Precentral  convolution,  function 

of            225 

Pregnancy,  diagnosis  of          .  .  19 

Prevention  of  shock  . .          . .  49 

Proteins,  absorption  of          . .  122 

Prothrombin     . .          . .          . .  132 

—  at  fault  in  haemophilia     . .  138 
Protopathic  sense        .  .          . .  185 

Purgatives,  action  of              . .  107 

Purin  bodies     . .          . .          . .  146 

Purinometer      . .          .  .          . .  152 

Pyloric  spasm  . .          .  .          . .  1 1 1 

Pylorus,  movements  of         . .  100 

—  stenosis  of  .  .          . .          . .  112 

Pyramidal  tract          . .          . .  201 

Pyrosis  . .  . .  . .  ..in 


Quadrilateral,  Marie's 


232 


Reaction  of  degeneration  after 

nerve  section    ..          ..  189 

Recurrent  sensibility  . .          .  .  19° 

Regeneration  of  nerve           . .  189 

—  not  in  the  spinal  cord  . .  211 
Rhubarb,  oxaluria  from  . .  152 
Rice  and  beri-beri  . .  . .  2 
Rickets,  cause  of  . .  .  .  5 
Robertson  and  Boyd  on  nutrient 

enemata             .  .          . .  128 

Rogers  on  cholera  . .  .  .  51 
Romberg  and  Passler  on  toxaemic 

shock      . .          . .          . .  31 

Roos  on  iodothyrin      . .          . .  77 

—  thyroid  feeding      . .           . .  74 
Rubrospinal  tract        . .        201,  226 
Ryffel    and    Laidlaw    on    nu- 
trient enemata            . .  126 


Sahli  on  haemophilia  .  .          .  .  138 

Salicylates  poisoning  .  .          . .  158 

Saline  transfusion        .  .          . .  51 

Salisbury  and  Rendle  Short  on 

cutaneous  anaesthetics  241 

S chafer  on  pituitary    . .          . .  91 

Scurvy,  cause  of          . .          .  .  4 

Secretin             . .          . .          .  .  118 

Seelig  and  Lyon  on  shock       .  .  24 

Segmental  areas,  table  of      . .  206 


PAGE 

Seidel  and  Hunt  on  iodothyrin  77 
Semicircular  canals  and  nys- 
tagmus . .          . .          . .  218 

Sensation,  conduction  in  spinal 

cord       . .          . .          . .  203 

—  localization  of  in  cortex    . .  220 

—  in  stomach  . .          . .          . .  108 

Sensibility,  recurrent  . .         . .  190 

Serum   of   horse,   for   hemor- 
rhagic tendency          . .  141 

Sharkey  on  nutrient  enemata  127 

Sherren  on  cutaneous  sensation  185 

—  nerve  suture           ..          ..  195 

—  gastric  ulcer  ..  ..  112 
Sherrington    on    concentration 

of  blood  in  shock         . .  36 

—  spinal  shock  . .          . .          . .  43 

Shock  absent  when  posterior 

nerve-roots  are  divided  199 

—  and  acapnia           . .          . .  26 

—  carbon  dioxide       . .          . .  26 

—  pituitary  extract  in  49,  96 

—  surgical        . .          . .          . .  21 

how  to  prevent           . .  48 

Shock,  toxaemic  . .  .  .  31 
Short,    Rendle,   on  division   of 

posterior    nerve-roote  200 

iodoform  and  thyroidism  81 

gastrojejunostomy       ..ii4n. 

nutrient  enemata         . .  127 

oxaluria             ..          ..  152 

surgical  shock   . .      35  et  seq. 

—  —  and  Salisbury,  on  cutan- 

eous anaesthetics      . .  241 

Sight,  cortical  localization  of . .  221 
Spasticitj7,  division  of  posterior 

nerve-roots  for  . .  201 
Spastic     paresis     in     cerebral 

tumour  . .  . .  235 
Specific    gravity   of   blood   in 

shock      . .          . .          . .  36 

Speech  centres..         ..          ..  230 

Spinal  cord,  ascending  tracts  of  202 

descending  tracts  of    .  .  201 

does  not  regenerate     . .  2 1  r 

injuries  of         .  .          . .  209 

tumours  of       . .          . .  203 

—  nerve-roots,  effects  of  divi- 

sion of  . .          . .          . .  199 

—  segmental  areas,  table  of  . .  206 
Squire,  case  of  haemophilia  . .  135  n. 
Starling  on  diabetic  heart      ..  168 

—  and  Bay  lis  s  on  secretin  ..  118 
Starr,    Allen,    on    tumours    of 

auditory  nerve            ..  219 

Starvation,  diagnosis  of          ..  163 

—  survival  in  .  .          ..          ..  129 

Statham  on  acidosis  of  preg- 
nancy    . .          . .          . .  161 

Stereognosis      ..          ..          ..  203 

Stewart-Harte  case     . .          . .  211 


INDEX 


253 


PAGE 

Stomach,  movements  of        . .  ioo 

Strychnine  for  shock  .  .          . .  49 
Stuart-Hart's    test   for   /3-oxy- 

but3Tric  acid      .  .          .  .  170 

Sudden  death  from  chloroform  177 

Suprarenals  and  shock           . .  40 

Sutton,  Bland,  on  rickets       . .  5 

Swallowing        . .          . .          . .  99 


Tactile  sense,  conduction  in 

spinal  cord 
Temperature,   in   cerebral   ab- 
scess 

—  sense,  conduction  in  spinal 

cord 
Temporal  lobe,  functions  of  . . 

Testis 

Tetany,  experimental 

—  treatment  of 
Thalamus,  lesions  of    . . 
Thiele  on  muscular  tone 
Thrombogen 
Thrombokinase 
Thyroid  colloid,   chemistry  of 

—  and  bone  formation 


effects  of  removal  of 


—  extract,  standardization  of 

—  feeding 

—  intoxication 

from  iodoform . . 

Tone,  Deiter's  nucleus  and 

—  in     diagnosis     of     cortical 

tumours 

—  influence  of  tracts  on 

—  loss    of    from    division    of 

posterior  nerve-roots 

—  lost  in  cerebellar  lesions 
Tone  and  shock 
Transfusion  for  haemophilia 

—  with  saline 
Transplantation  of  bone 

—  nerve 
Treatment  of  acetonaemia 

—  acidosis 

—  acromegaly .  . 

—  beri-beri 

—  to  prevent  calculus  15 

—  of  chilblains 

—  chloroform  poisoning 

—  late  chloroform  poisoning 

—  cholera 

—  cyclical  vomiting  .  . 

—  delayed  puberty    . . 

—  diabetic  coma 

—  to  prevent  diabetic  coma. 
■ —  of  facial  palsy 

—  fractures 

—  gastric  carcinoma 

—  —  crises 

—  —  ulcer 


203 

228 

203 

220 

12 

72 

84 

225 

226 

132 

132 

74 

68 

7o,  73 


86 
74 
83 
80 
226 

235 
203 

199 
217 

45 
142 

5i 

67 
196 
172 
172 

95 
2 

154 
144 

179 

182 

5i 

172 

15 
176 

173 
197 
65 
119 
201 
"3 


Treatment  after  gastrostom 

—  of  gigantism 

—  Graves'  disease 

—  haemophilia .  . 

—  haemorrhagic    tendency    in 

jaundice 

—  hyperchlorhydria   . . 

—  infantile    palsy    by    nerve 

anastomosis 

—  infantilism  . . 

—  intestinal  paralysis  106, 

—  lymphatic  headache 

—  to  prevent  meningitis 

—  of  myositis  ossificans 

—  myxcedema 

—  nerve  injuries         . .        189, 

—  by  nutrient  enema ta       126, 

—  of  oxaluria . . 

—  painful  inoperable  cancer 

—  pancreatic  fistulse .  . 

—  post-anaesthetic  vomiting 

—  by  saline  transfusion 

—  of  shock 

—  spasticity 

—  transient  albuminuria 

—  tetany  . .  . .  I 

—  uric  acid  deposit    . . 

—  urticaria 
Trephining,     palliative,      for 

tumour 
Trophic  changes,  cause  of 

from   division   of   post 

nerve  roots  .  . 
Trotter  on  nerve  suture 
Tumour   of   brain,   misleading 

localizing  signs  of 
Tumours   in   cerebello-pontine 

angle 

—  of  cortex,  localization  of 

—  spinal  cord 
Twins 


pace 

118 

95 

85 

140 

139 
113 

198 

95 

107 

144 

237 

65 

84 

196 

245 

154 

201 

121 

182 

5i 

49 

175 

144 

144 

151 

144 

215 
187 

199 
195 

234 

219 
230 
203 

Q 


Ulnar  palsy,  symptoms  of  .  .  185 

Urates,  origin  of,  in  the  bod}7  145 

Uric  acid,  origin  of,  in  body.  .  145 

—  —  deposit,  treatment  of  .  .  151 

Urticaria,  treatment  of  . .  r44 


Vale  on  shock..          ..          ..  35 

Vasomotor  reflexes      ..          ..  187 

Venous  pressure  in  acapnia  . .  32 

Vestibulospinal  tract  . .          .  .  202 

Vision,   cortical  localization  of  221 

Visual  word  centre      . .          .  .  231 

Vitamines          .  .          . .          . .  1 

Vomiting,      prolonged,      after 

chloroform        . .          . .  182 

Von  Noorden  on  diabetic  coma  174 
pancreatic  diabetes     . .  169 


54 


INDEX 


Wallerian  degeneration  in 
nerve  fibres      . .        185, 

spinal  tracts 

Walton  on  intestinal  shock    . . 

Warrington  on  division  of 
posterior  nerve-roots  . . 

—  and  Murray  on  nerve  anas- 

tomosis    for     infantile 
palsy 
Water,  absorption  of  by  bowel 

—  supply  and  goitre 
Watson,  Chalmers,  on  goitre  . . 


194 
175 
106 

200 


198 

125 

75 

76 


Weil    on     horse     serum  for 

haemophilia  . .  . .  141 
Wells  on  iodothyrin  . .  . .  75 
Wells  and  goitre  . .  . .  75 
Willcox  on  gastric  HC1  . .  109 
—  infantile  dyspepsia  . .  1 1  r 
Wright,  Sir  A  Imroth,  on  haemo- 
philia     . .          . .  136,  141 


Xanthin  . .  . .        146,  r  48 

X-tays  in  mapping  out  stomach    100 


1207.14  JOHN    WRIGHT   AND   SONS   LTD.,    PRINTERS,    BRISTOL 


255 


ADDENDUM. 

The  Acidity  of  Gastric  Juice. — An  interesting 
sell-regulating  mechanism  of  the  acidity  of  the  gastric 
juice  has  recently  been  described.  As  secreted,  in 
animals  and  man,  the  hydrochloric  acid  is  as  much 
as  0-5  per  cent,  but  it  is  neutralized,  partly  by  food 
and  partly  by  the  regurgitation  of  pancreatic  and 
intestinal  juices,  down  to  0'2  or  o-i  per  cent,  which 
is  the  optimum,  and  in  health  it  is  maintained  at 
this  standard.  In  hyperchlorhydiia,  this  regulation 
breaks  down,  and  the  acidity  approximates  to  0*5 
per  cent. 

The  Nervous  Control  of  Muscular  Tone. — 
A  very  interesting  research  has  been  published  by 
Weed,  affording  a  different  explanation  from  that 
given  in  the  text  with  reference  to  the  nervous  control 
of  muscular  tone.  This  has  an  important  bearing  on 
the  explanation  not  only  of  the  rigidity  which  is  seen 
in  the  body  and  limbs  of  cats  after  section  of  the 
mesencephalon  (decerebrate  rigidity),  but  also  of  that 
which  accompanies  hemiplegia  or  monoplegia  in  man, 
and  the  occurrence  of  atonia  in  cerebellar  lesions. 

According  to  Weed's  researches  on  cats,  the  centre 
which  is  responsible  for  the  exaggeration  of  muscular 
tone  is  the  red  nucleus,  and  it  does  so  in  response  to 
sensory  stimuli  reaching  it  from  the  posterior  nerve 
roots  by  way  of  the  ventral  cerebellar  tract,  cere- 
bellum,  and  superior  cerebellar  peduncle.     Section 


256  ADDENDUM 

of  any  of  the  following  will  abolish  decerebrate 
rigidity  :  the  posterior  nerve  roots,  anterolateral 
region  of  the  cord,  superior  cerebellar  peduncle,  or 
any  part  of  the  brain-stem  below  the  red  nucleus. 
Ablation  of  the  cerebellum  or  of  the  cerebellar  cortex 
also  abolishes  tone.  Cutting  the  inferior  cerebellar 
peduncle  or  the  columns  of  Goll  and  Burdach  do  not 
influence  it.  It  will  be  remembered  that  the  ventral 
cerebellar  tract  enters  by  the  superior  peduncle. 

On  the  other  hand,  the  inhibitory  path  cut  oft  when 
the  mesencephalon  is  divided  is  supposed  to  be  the 
fronto-pontic  tract  and  middle  cerebellar  peduncle. 
Stimulation  of  either  of  these  inhibits  any  excess  of 
muscular  tone. 

The  exact  location  of  the  tone  centre  probably  has 
an  important  bearing  upon  the  pathology  of  surgical 
shock. 


